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Purpose: Proliferative diabetic retinopathy (PDR) can be treated by retinal photocoagulation, but in some cases, the treatment is initiated too late or is insufficient so that the disease advances to a stage requiring vitrectomy. There is a need to identify risk factors that can predict if patients with PDR will develop complications in need for vitrectomy. Methods: Survival analysis with death as competing risk was used to study systemic risk factors for PDR progression to a complication in need for vitrectomy in right eyes of all 1288 diabetic patients from the Aarhus area, Denmark, who had developed proliferative retinopathy in the right eye during the 25 years period from 1 July 1994 until 1 July 2019. Results: The overall cumulative incidence of reaching a vitrectomy end point in the right eye was 24.1% (n = 311). In 9.3% (n = 120) of the patients where vitrectomy had been performed together with the first photocoagulation, the age of onset of diabetes was significantly higher (p < 0.0001), the diabetes duration longer (p < 0.035) and BMI higher (p < 0.01) than in the patients who had been vitrectomized later than the first photocoagulation. The risk for vitrectomy was significantly increased by high variability of HbA1c before the development of PDR (p < 0.0001), but not by other parameters known to increase the risk for developing PDR. Conclusion: Increasing variability of HbA1c before the development of PDR increases the risk for progression to a complication in need of vitrectomy. The need for vitrectomy is unaffected by other risk factors known to increase the risk for developing PDR.

As clinical practice variation has been problematized as a symptom of suboptimal care and inefficient resource spending, consistency in the delivery of healthcare is a recurring policy goal. We examine a case where the introduction of a new treatment is most likely to provide consistency in healthcare delivery because it was introduced with a national clinical practice guideline representing consensus about best clinical practice among leading clinicians, and because care delivery was highly centralized to few high-volume treatment units. Despite the consensus on best clinical practice and care centralization, this study shows pronounced regional variation in patient outcomes and treatment costs that increased over time. Using a mixed-methods design, we find that the lack of consistency in care was largely unrelated to patient-specific characteristics, but seemed to reflect structural differences in the regional organization and financing of healthcare delivery. We conclude that the value of clinical practice guidelines is undermined when structural barriers limit the ability of clinicians and clinical managers to scale up treatment, and that some degree of decentralization may be a tool to maintain treatment intensity when the treatment effect is dependent on a high treatment intensity.

Background:To assess the prevalence of macular microcystoid lacunae in patients with autosomal dominant optic atrophy (ADOA) and its association with visual function and inner retinal morphology.Methods:The study included 140 participants with ADOA, with a mean age of 44 (SD ±19, range 7-82) years. Study participants with a genetically verified sequence variant in the OPA1 gene were examined with best-corrected visual acuity, contrast sensitivity, optical coherence tomography (Spectralis, Heidelberg) and adaptive optics fundus photography (rtx1, Imagine Eyes). Optically empty microcystoid spaces in the ganglion cell layer and inner plexiform layer were mapped by inspection of the 2 sets of images. Data were analyzed with a mixed model adjusted for age and sex with family and individual as random effect.Results:Microcystoid lacunae were present in 32 of 140 participants (23%) including 18 males and 14 females. Microcystoid lacunae were associated with younger age (P = 0.0503) and a smaller nerve fiber layer volume (P = 0.035). No association was found between presence of microcystoid lacunae and visual acuity (P = 0.2), contrast sensitivity (P = 0.8), axial length (P = 0.7), or ganglion cell layer volume (P = 0.2). The analysis showed moderately reduced visual acuity in patients with microcystoid lacunae. Normal and severely impaired visual function were seen only in participants without microcystoid lacunae.Conclusion:In ADOA, macular microcystoid lacunae were found in 23% of the study participants and tended to be present in younger participants with moderate visual acuity reduction and a smaller nerve fiber layer volume. Further studies are needed to investigate whether cavities left by dead ganglion cells are predictors of decrease in visual function.

PURPOSE: This study seeks to examine potential risk factors for the development of retinal artery occlusions (RAO).METHODS: We used data obtained from Danish nationwide registries to evaluate potential risk factors for RAO present up to 5 years prior to the RAO diagnosis. The study included 5312 patients diagnosed with RAO registered in the Danish National Patient Register and 26,560 controls assessed from the general population matched on sex and age at index date. Adjusted conditional logistic regression was used to estimate the odds ratio of included risk factors for RAO diagnosis. We conducted supplementary analyses stratified on sex and age, and on RAO subtype. In addition, interaction analyses were performed between strata in the stratified analyses.RESULTS: Risk factors associated with the development of RAO included diabetes, arterial hypertension, ischemic heart disease, peripheral artery disease, stroke, renal disease, cataract, and glaucoma, with ORs ranging from 1.33 to 4.94. Atrial fibrillation and sleep apnea yielded effect measures close to equivalence. The presence of a risk factor was generally associated with higher odds of RAO among the population ≤ 55 of age. Arterial hypertension was stronger associated with RAO in male patients than in female patients. The association with arterial hypertension was stronger for CRAO than for BRAO subtype.CONCLUSION: The investigated risk factors suggest that atherosclerosis and conditions changing the intraocular pressure are involved in the pathophysiology of RAO.

Background: Retinal artery occlusion (RAO) has been considered a stroke equivalent. This study compares risk factor profiles for thromboembolism among patients with RAO and stroke, respectively. Methods: This case-control study is based on 5683 RAO patients entered in the Danish National Patient Register between 1st of January 2000 and 31st of December 2018. Cases were matched on sex, year of birth, and age at event with 28,415 stroke patients. The Danish nationwide registries were used to collect information about age, sex, previous diagnoses, and drug prescriptions. Adjusted conditional logistic regression models were used to investigate the association between hypothesised risk factors and the patient outcome. Results: For atrial fibrillation, a substantially stronger association to stroke was found, with an odds ratio (OR) of 0.52 (95% CI: 0.47-0.58) when comparing RAO patients with stroke patients. RAO was stronger associated with arterial hypertension, peripheral artery disease, retinal vein occlusion, cataract, and glaucoma with OR's ranging from 1.21-11.70. The identified effect measures reached equivalence or was close to equivalence for diabetes, heart failure, ischemic heart disease, and renal disease. Conclusion: The differences in risk factor profiles between RAO and stroke suggests differences in the pathophysiology of the two diseases. These variations in pathophysiologies between the two diseases may indicate that different interventions are needed to ensure the optimal long-term prognosis for the patients.

IMPORTANCE: Thyroid eye disease (TED) is a serious condition that can cause proptosis and strabismus and, in rare cases, lead to blindness. Incidence data for TED and strabismus and surgical interventions after TED are sparce. OBJECTIVE: To investigate the nationwide incidence of TED, strabismus, and surgical interventions associated with TED. DESIGN, SETTING, AND PARTICIPANTS: A Danish nationwide registry-based cohort study between 2000, which marks the beginning of uniform coding for the decompression surgery nationwide, and 2018. The cohort consisted of a mean 4.3 million people aged 18 to 100 years with no prior TED diagnosis each year. Total observation time was 8.22 × 10(7) person-years (women, 4.18 × 10(7) person-years; men, 4.04 × 10(7) person-years). MAIN OUTCOME MEASURES: The annual numeric and age-standardized incidence of hospital-treated TED and cumulative incidence of strabismus, strabismus surgery, and orbital decompression surgery in patients with TED. The incidence was stratified by sex, thyroid diagnosis, and age. RESULTS: A total of 4106 incident diagnoses of TED were identified during 19 years among 3344 women (81.4%) and 762 men (18.6%). The mean numeric annual nationwide incidence rate of TED was 5.0 per 100 000 person-years overall, 8.0 per 100 000 person-years in women, and 1.9 per 100 000 person-years in men, resulting in a 4:1 ratio of women to men with TED. The age-standardized incidence was similar. The mean (SD) age at onset was 51.3 (14.5) years. At the time of TED diagnosis, 611 patients (14.9%) were euthyroid, 477 (11.6%) were hypothyroid, and 3018 (73.5%) were hyperthyroid. In patients with TED who were euthyroid, the 4-year cumulative incidence was 41% for antithyroid medication and 13% for L-thyroxine. In patients with TED, the 4-year cumulative incidence for strabismus was 10%. The 4-year cumulative incidence of surgical interventions after TED was 8% for strabismus surgery and 5% for orbital decompression. At 4 years, strabismus surgery was more common in men (13.3%; 95% CI, 10.75-15.86) than in women (7.2%; 95% CI, 6.24-8.08), and the absolute difference was 6.1% (95% CI, 3.42-8.14; P

Purpose: Previous studies have shown that the retinal oxygen saturation in central retinal vein occlusion treated with anti-VEGF compound has no predictive value for visual outcome after 12 months. It is of interest to evaluate whether this conclusion is similar for patients with branch retinal vein occlusion among whom only some patients are treated. Methods: Retinal oxygen saturation, visual acuity and central retinal thickness were studied at the time of referral and after six and 12 months in 111 patients successively referred to the Department of Ophthalmology, Aarhus University Hospital, with a venous occlusion affecting branches peripheral from the central retinal venule. The predictive value of the oxygen saturation at referral was investigated in treated and untreated patients. Results: Seventy-three patients with visual acuity between 35 and 70 ETDRS letters at referral were treated with intravitreal injection of anti-VEGF compound. Over 12 months, the venous oxygen saturation improved in parallel with central retinal thickness and visual acuity but had no predictive value for visual outcome. In 12 untreated patients with visual acuity >70 ETDRS letters, younger age and high oxygen saturation at the time of referral were positive predictors for the visual outcome after 12 months. Conclusion: Oxygen saturation, visual acuity and central retinal thickness improve in parallel during treatment of branch retinal vein occlusion with intravitreal anti-VEGF medication. Retinal oximetry at referral cannot predict visual acuity after 12 months in treated patients but may perhaps become a tool for predicting the visual prognosis in a subgroup of patients where treatment is omitted because of a too high visual acuity at the time of diagnosis of the disease.

Purpose: To identify parameters that can predict the postoperative risk for progression of retinopathy to a vision-threatening stage after cataract surgery. This may optimize the timing of surgery and the postoperative follow-up strategy in diabetic patients. Methods: Multi-state survival analysis with death as competing risk was used to investigate how year of onset and age of onset of diabetes, gender, body mass index, HbA1c and blood pressure had affected the risk for developing diabetic macular oedema (DME) and proliferative diabetic retinopathy (PDR) among 2540 right eyes from 2797 diabetic patients operated for cataract on one or both eyes during 25 years until July 1. 2019. Results: Cataract surgery had been performed in 98.8% of patients reaching 90 years of age. The risk for developing both DME and PDR was increased by cataract surgery. The risk was highest during the first postoperative years and increased by pre-operative variability in HbA1c. The risk after more than 20 years postoperatively increased by increased cumulative HbA1c pre-operatively. The other studied risk factors contributed differently to the development of the two complications. Conclusions: Decision models for the timing of cataract surgery in diabetic patients should consider that the risk for developing vision-threatening retinopathy depends on follow-up time. Differences in the risk profiles for developing DME and PDR after cataract surgery support that the two complications should be regarded as separate late complications.

Purpose: Clustering of vision threatening diabetic retinopathy within specific families can be the result of similarities in life style but may also be due to a common genetic background. An evaluation of the role of heredity for the development of diabetic retinopathy may help adjusting control intervals in screening program to each patient's individual risk profile. Methods: Survival analysis was used to study whether family history of diabetes among men and women with type 1 or type 2 diabetes together with the degree of heredity could be added as risk factors to improve the prediction of the risk for developing proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME). The study was conducted on data from 12,281 patients followed in the Aarhus area, Denmark, from 1 January 2003 to 1 July 2019. Results: The risk for developing PDR was significantly reduced 2–11 years after known onset of diabetes in the presence of female family members with type 1 diabetes, and the risk for developing DME significantly increased 4–24 years after onset of diabetes in the presence of family members with type 2 diabetes of any sex. These hereditary factors were independent of other studied risk factors such as previous cataract surgery, age of onset of diabetes, metabolic regulation and blood pressure. Conclusions: The presence of family members with diabetes affects the risk for developing vision threatening diabetic retinopathy and affects the risk for developing PDR and DME differently. This evidence may help individualizing the control intervals in screening programmes for diabetic retinopathy.

Cognitive impairment; Diabetes mellitus; Diabetic retinopathy Discapacidad cognitiva; Diabetes mellitus; Retinopatía diabética Discapacitat cognitiva; Diabetis mellitus; Retinopatia diabètica Background: Retinal neurodegeneration is evident in early diabetic retinopathy (DR) which may be associated with other neurodegenerative diseases like Alzheimer's disease (AD). Objective: To investigate diabetes and DR as a risk marker of present and incident AD. Methods: A register-based cohort study was performed. We included 134,327 persons with diabetes above 60 years of age, who had attended DR screening, and 651,936 age- and gender-matched persons without diabetes. Results: At baseline, the prevalence of AD was 0.7% and 1.3% among patients with and without diabetes, respectively. In a multivariable regression model, patients with diabetes were less likely to have AD at baseline (adjusted OR 0.63, 95% CI 0.59–0.68). During follow-up, incident AD was registered for 1473 (0.35%) and 6,899 (0.34%) persons with and without diabetes, respectively. Compared to persons without diabetes, persons with diabetes and no DR had a lower risk to develop AD (adjusted HR 0.87, 95% CI 0.81–0.93), while persons with diabetes and DR had higher risk of AD (adjusted HR 1.24, 95% CI 1.08–1.43). When persons with diabetes and no DR were used as references, a higher risk of incident AD was observed in persons with DR (adjusted HR 1.34, 95% CI 1.18–1.53). Conclusion: Individuals with diabetes without DR were less likely to develop AD compared to persons without diabetes. However, individuals with DR had a 34% higher risk of incident AD, which raise the question whether screening for cognitive impairment should be done among individuals with DR. This work was supported by VELUX FONDEN (grant number 00028744) and Odense University Hospital PhD Foundation (grant number 4339).

INTRODUCTION: Risk factors for retinal vein occlusion have been extensively studied, with varying population sizes. Smaller populations result in less certain measures of associations. The present review included studies with a relevant population size to identify clinically relevant risk factors for retinal vein occlusion. Understanding the risk factors of retinal vein occlusion is important for the management of these patients.AREAS COVERED: A comprehensive literature review was conducted through a systematic literature search in PubMed and Embase. Additional studies were selected from cross references in the assessed studies. Weighted effect measures were calculated for all included risk factors.Risk factors associated with retinal vein occlusion included cardiovascular diseases, eye diseases, systemic diseases, medical interventions, and sociodemographic factors.EXPERT OPINION: This review provided an extensive overview of a wide variety of risk factors increasing the risk of developing retinal vein occlusion. The severity of the identified risk factors indicated that these patients have been in contact with the health care system before their retinal vein occlusion event. Therefore, the clinical course for patients with retinal vein occlusion may benefit from a multidisciplinary collaboration between ophthalmologists and especially cardiologists.

Purpose: The purpose of the study was to evaluate vision-related quality of life and visual ability in patients with OPA1 autosomal dominant optic atrophy (ADOA). Methods: This cross-sectional, observational study included 145 participants with a mutation in the OPA1 gene associated with ADOA, 63 mutation-free first-degree relatives and 92 healthy subjects unrelated to the families. Participants underwent a clinical eye examination, and adult participants completed the National Eye Institute Visual Function Questionnaire (NEI-VFQ-39), while children completed the Cardiff Visual Ability Questionnaire for Children (CVAQC). Results: In adults with ADOA, both mean visual acuity (VA) and mean contrast sensitivity (CS) were significantly inferior to both first-degree relatives and unrelated controls (p < 0.001). In children with ADOA, mean VA was significantly lower compared with first-degree relatives (p = 0.0052), whereas CS was not (0.127). Adults with ADOA scored lower than both comparator groups on composite score (p < 0.001), general health subscale (p = 0.0075) and all vision-related subscales (p < 0.001) except the ocular pain subscale (p = 0.2). In children with ADOA, the median CVAQC logit score was significantly lower compared with first-degree relatives (p = 0.037). The science lessons subscale was significantly lower for children with ADOA compared with first-degree relatives (p = 0.046), as well as the language lessons subscale (p = 0.038). For adults, composite score and subscale scores were significantly associated with both VA, CS and fixation status. Conclusion: OPA1 mutation is associated with lower quality of life and visual ability in patients with ADOA compared with both first-degree relatives and unrelated controls. VA, CS and fixation status affect quality of life in patients with ADOA.

This study seeks to examine potential risk factors for the development of retinal artery occlusions (RAO).We used data obtained from Danish nationwide registries to evaluate potential risk factors for RAO present up to 5 years prior to the RAO diagnosis. The study included 5312 patients diagnosed with RAO registered in the Danish National Patient Register and 26,560 controls assessed from the general population matched on sex and age at index date. Adjusted conditional logistic regression was used to estimate the odds ratio of included risk factors for RAO diagnosis. We conducted supplementary analyses stratified on sex and age, and on RAO subtype. In addition, interaction analyses were performed between strata in the stratified analyses.Risk factors associated with the development of RAO included diabetes, arterial hypertension, ischemic heart disease, peripheral artery disease, stroke, renal disease, cataract, and glaucoma, with ORs ranging from 1.33 to 4.94. Atrial fibrillation and sleep apnea yielded effect measures close to equivalence. The presence of a risk factor was generally associated with higher odds of RAO among the population ≤ 55 of age. Arterial hypertension was stronger associated with RAO in male patients than in female patients. The association with arterial hypertension was stronger for CRAO than for BRAO subtype.The investigated risk factors suggest that atherosclerosis and conditions changing the intraocular pressure are involved in the pathophysiology of RAO.

BACKGROUND AND AIMS: Attenuated retinal vasoreactivity in patients with type 2 diabetes preceding diabetic retinopathy development has been proposed to reflect local endothelial dysfunction. Whether retinal vessel reactivity is associated with peripheral endothelial dysfunction and large artery stiffness in patients with type 2 diabetes remains to be elucidated.METHODS: Twenty patients with type 2 diabetes without retinopathy and 20 sex- and age matched controls (diabetes duration: 9.9 years (range 6.0;12.4), 40% male, age: 66.5 ± 7.3 (diabetes) and 65.2 ± 7.6 years (controls)) were included. Endothelial function was assessed using EndoPAT. Arterial stiffness was assessed by carotid-femoral pulse wave velocity using the SphygmoCor. Retinal blood supply regulation was examined by retinal arteriolar diameter change during 1) isometric exercise (hand-weight lifting), 2) exposure to flickering lights, and 3) a combined stimulus of 1) + 2) using the Dynamic Vessel Analyzer.RESULTS: No significant differences were observed in retinal vessel reactivity in T2DM patients compared to controls. Endothelial function was associated with mean arteriolar diameter change during only the combination intervention, (Beta = 0.033 [0.0013;0.064], p = 0.042) in the overall population of patients and controls. When groups were analyzed separately, the associations was statistically significant only in controls. However, formal test for interaction was not statistically significant, p = 0.40. No association was observed between pulse wave velocity and retinal arteriolar %-diameter change in patients or controls.CONCLUSION: Peripheral endothelial function was associated with retinal arteriolar diameter change in the combined sample. The association seemed to be driven primarily by the controls. Our findings indicate that peripheral endothelial function is reflective of endothelial function in the retina mainly in subjects without T2DM, whereas an association in T2DM without retinopathy was not observed. Further studies are needed in T2DM patients with more advanced retinopathy.

PURPOSE. Convergence insufficiency (CI) is characterized by abnormal vergence eye movement frequently accompanied by abnormal accommodation and subjective symptoms, such as headache, blurred vision, and diplopia. CI is treated with vergence and accommodation exercises that are integrated so that the relative contributions of vergence and accommodation exercises to the outcome are concealed. The purpose of the present study was to determine the individual contributions of vergence and accommodation exercises for the treatment of CI in school children. METHODS. In a prospective crossover study 44 children aged 9 to 13 years with CI were randomized to perform either vergence exercises followed by accommodation exercises each for 6 weeks or the 2 treatment regimes in the reverse order. The outcome measures were recovery from CI and the parameters vergence facility, positive fusional vergence, near point of convergence, monocular amplitude, and facility of accommodation. RESULTS. After the first 6-week period, full recovery from CI was significantly more frequent in the group commencing vergence exercises than in the group commencing monocular accommodation exercises (p = 0.01), whereas there was no significant difference between these proportions after the second 6-week period (p = 0.45). Vergence facility and positive fusional vergence improved significantly more after the period with vergence exercises than after the accommodation exercises, whereas there was no significant difference between the effects of the two types of exercises on the other studied parameters. CONCLUSIONS. Vergence treatment induces a faster recovery of CI than accommodation treatment in school children. This may be used to improve compliance and success rate of the treatment.

PURPOSE. Recent evidence suggests that the smaller retinal vessels are significantly involved in the regulation of retinal blood flow and that this regulation may differ among the macular area and the retinal periphery. An alternative to studying blood flow regulation in smaller retinal vessels that are difficult to resolve is to assess the metabolic consequences of changes in the microcirculation using oximetry. METHODS. In 20 normal persons aged (mean ± SD, range) 30.1 ± 3.8 (24-37) years, the oxygen saturation and diameter of retinal arterioles and venules to the macular area and the retinal periphery were studied before and during an increase in the arterial blood pressure induced by isometric exercise. RESULTS. The isometric exercise increased the mean arterial blood pressure by (mean ± SEM) 10.0 ± 1.1 mm Hg but induced no significant changes in the diameter of the arterioles (P = 0.83). The isometric exercise had no significant effect on the oxygen saturation in the arterioles supplying the macular area and the retinal periphery (P > 0.42 for both comparisons). However, there was a significant increase in the oxygen saturation in venules draining the retinal periphery to reduce the oxygen extraction from (mean ± SEM) 36.0% ± 2.3% to 30.6% ± 2.1% (P = 0.002) but no significant change in the preexisting low oxygen extraction in the macular area that changed from (mean ± SEM) 18.2% ± 3.0% to 16.2% ± 1.9% (P = 0.37). CONCLUSIONS. Minor changes in the arterial blood pressure can induce changes in retinal rheology with significant regional variation. The finding may help explain regional variations in manifestations of retinal vascular disease such as hyperpermeability in the macular area and capillary occlusion in the retinal periphery.

Purpose: Central retinal vein occlusion (CRVO) entails retinal hypoxia that often causes visual impairment. It has been shown that oxygen saturation in larger retinal vessels correlates with the visual acuity at the time of diagnosis of CRVO but has no predictive value for the visual outcome in patients treated with anti-VEGF medication after 3 months. However, assessing the predictive value of retinal oxygen saturation after 12 months is essential because this is when the main restitution after CRVO occurs. Methods: Retinal oximetry was performed in 117 patients referred with CRVO to three European centres. The correlation between oxygen saturation and visual acuity at baseline and the predictive value of oxygen saturation in larger retinal vessels for the 12-month visual outcome after treatment with anti-VEGF medication were studied. Results: In the affected eye, the oxygen saturation was significantly higher in the arterioles, significantly lower in the venules, and the arterio-venous (A-V) significantly higher than in the unaffected eye (p

INTRODUCTION: Diabetic retinopathy is defined as morphological lesions in the retina secondary to diabetes. The lesions may progress to a vision-threatening stage, which is more frequent in men and people with weak personal networks and a low psychosocial status. However, there is limited knowledge about the influence of other socio-economic factors on the development of treatment-requiring diabetic retinopathy.METHODS: The number of patients from each postal district in the Aarhus County area who had been treated for diabetic retinopathy in the first eye between 1 July 1994 and 1 July 2019 was acquired. The standard information package "Key figures from postal districts" published 1 October 2019 by Statistics Denmark was used to study differences in treatment rates of diabetic retinopathy among postal districts and to explore to which extent such differences may be explained by population size, age, educational background and income.RESULTS: During the study period of 25 years, 2,142 patients with home address in the former Aarhus County were treated for diabetic retinopathy. The treatment rate showed marked geographical variations and was inversely related to educational level, but was not independently related to either population size, age or income.CONCLUSIONS: Initiatives aiming to reduce the incidence of treatment-requiring diabetic retinopathy in Danish healthcare should include preventive measures especially adapted to citizens with a low educational background. FUNDNG: none.TRIAL REGISTRATION: not relevant.

Purpose: Diabetic maculopathy (DM) treated with photocoagulation may subsequently progress to proliferative diabetic retinopathy (PDR). However, there is insufficient knowledge about the incidence and risk factors for the development of PDR in patients previously treated for DM. Materials and methods: Survival data was used to analyze prospectively collected epidemiological and clinical data to describe the incidence and risk factors for the occurrence of PDR in all 1,235 patients photocoagulation treated for DM in a defined population from the Aarhus area, Denmark, from January 1. 1993 until December 31. 2016. Results: Among 1,204 (97.5%) of the patients in whom the subsequent clinical history was known, 536 (44.5%) had died and 131 (10.9%) had received panretinal photocoagulation for PDR. The cumulative incidence of developing PDR after photocoagulation for diabetic maculopathy increased with time to reach a plateau around 13% after approximately 15 years. Earlier age at diagnosis of diabetes and higher HbA1c at the time of macular treatment were significant risk factors for the development of PDR, whereas gender, diabetes type, body mass index, known diabetes duration at the time of macular photocoagulation and blood pressure were not significant risk factors. Conclusions: In patients treated with retinal photocoagulation for DM, a tight metabolic control is accompanied with a reduced risk for subsequent progression to PDR. In the treated patients who do not develop PDR, the control interval can be gradually increased with time.

PURPOSE: Diabetic retinopathy (DR) is among the leading causes of visual loss in the working-age population. It is generally accepted that screening of DR is cost-effective and can detect DR before it becomes sight-threatening to allow timely treatment.METHODS: A group of retinal specialists was formed by the Danish Ophthalmological Society with the aim to formulate contemporary evidence-based guidelines for screening of DR in order to implement these in the Danish screening system.RESULTS: We hereby present evidence for DR-screening regarding (1) classification of DR, (2) examination techniques, (3) screening intervals and (4) automated screening. It is our recommendation that the International Clinical Retinopathy Disease Severity Scale should be used to classify DR. As a minimum, mydriatic two-field disc- and macular-centred images are required. In the case of suspected clinically significant diabetic macular oedema, supplementary optical coherence tomography can increase the diagnostic accuracy. There is solid evidence to support a flexible, individualized screening regimen. In particular, it is possible to prolong screening intervals to 24-48 months for patients with no or mild nonproliferative diabetic retinopathy (NPDR), but it is also possible to use extended intervals of 12-24 months for patients with moderate NPDR given that these are well-regulated regarding glycaemic control (HbA1c ≤ 53 mmol/mol) and blood pressure (≤130/80 mmHg). Automated screening of DR is encouraging but is not ready for implementation at present.CONCLUSION: Danish evidenced-based guidelines for screening of DR support high-quality imaging and allow flexible, individualized screening intervals with a potential for extension to patients with low risk of DR progression.

PURPOSE: Diabetic maculopathy can be treated with intravitreal injection of vascular endothelial growth factor (VEGF) inhibitors. However, the therapy is not effective in all patients, and it would be desirable to have parameters for differentiating patients who will benefit from treatment from those who will not. Retinal fixation has been shown to be impaired in patients with low visual acuity (VA) secondary to macular disease, but the changes in fixational eye movements after anti-VEGF treatment for diabetic maculopathy have not been investigated.METHODS: Retinal fixation was studied in 29 patients with diabetic macular oedema before three monthly anti-VEGF injections, and 1 and 4 months after the last injection. The change in VA was correlated with changes in area, frequency, amplitude and total number of fixational saccades.RESULTS: During three monthly injections, best-corrected visual acuity (BCVA) increased from (mean ± SD) 74.0 ± 11.5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters to 78.3 ± 9.8 ETDRS letters, (p = 0.003) and central retinal thickness (CRT) decreased from (mean ± SD) 441.7 ± 107.0 μm to 339.5 ± 74.2 μm, (p = CONCLUSION: Fixational eye movements may be used to monitor short-term effects of anti-VEGF treatment on diabetic macular oedema. Future studies should aim at investigating a possible predictive value of fixational eye movements for visual function in the long term.

International audience; Cerebellar ataxia, areflexia, pes cavus, optic atrophy and sensorineural hearing impairment (CAPOS) is a rare clinically distinct syndrome caused by a single dominant missense mutation, c.2452G\textgreaterA, p.Glu818Lys, in ATP1A3, encoding the neuron-specific alpha subunit of the Na+/K+-ATPase α3. Allelic mutations cause the neurological diseases rapid dystonia Parkinsonism and alternating hemiplegia of childhood, disorders which do not encompass hearing or visual impairment. We present detailed clinical phenotypic information in 18 genetically confirmed patients from 11 families (10 previously unreported) from Denmark, Sweden, UK and Germany indicating a specific type of hearing impairment-auditory neuropathy (AN). All patients were clinically suspected of CAPOS and had hearing problems. In this retrospective analysis of audiological data, we show for the first time that cochlear outer hair cell activity was preserved as shown by the presence of otoacoustic emissions and cochlear microphonic potentials, but the auditory brainstem responses were grossly abnormal, likely reflecting neural dyssynchrony. Poor speech perception was observed, especially in noise, which was beyond the hearing level obtained in the pure tone audiograms in several of the patients presented here. Molecular modelling and in vitro electrophysiological studies of the specific CAPOS mutation were performed. Heterologous expression studies of α3 with the p.Glu818Lys mutation affects sodium binding to, and release from, the sodium-specific site in the pump, the third ion-binding site. Molecular dynamics simulations confirm that the structure of the C-terminal region is affected. In conclusion, we demonstrate for the first time evidence for auditory neuropathy in CAPOS syndrome, which may reflect impaired propagation of electrical impulses along the spiral ganglion neurons. This has implications for diagnosis and patient management. Auditory neuropathy is difficult to treat with conventional hearing aids, but preliminary improvement in speech perception in some patients~suggests that cochlear implantation may be effective~in CAPOS patients.

Aims/hypothesis\ud Diabetic retinopathy is characterised by morphological lesions related to disturbances in retinal blood flow. It has previously been shown that the early development of retinal lesions temporal to the fovea may predict the development of treatment-requiring diabetic maculopathy. The aim of this study was to map accurately the area where lesions could predict progression to vision-threatening retinopathy.\ud \ud Methods\ud The predictive value of the location of the earliest red lesions representing haemorrhages and/or microaneurysms was studied by comparing their occurrence in a group of individuals later developing vision-threatening diabetic retinopathy with that in a group matched with respect to diabetes type, age, sex and age of onset of diabetes mellitus who did not develop vision-threatening diabetic retinopathy during a similar observation period.\ud \ud Results\ud The probability of progression to vision-threatening diabetic retinopathy was higher in a circular area temporal to the fovea, and the occurrence of the first lesions in this area was predictive of the development of vision-threatening diabetic retinopathy. The calculated peak value showed that the risk of progression was 39.5% higher than the average. There was no significant difference in the early distribution of lesions in participants later developing diabetic maculopathy or proliferative diabetic retinopathy.\ud \ud Conclusions/interpretation\ud The location of early red lesions in diabetic retinopathy is predictive of whether or not individuals will later develop vision-threatening diabetic retinopathy. This evidence should be incorporated into risk models used to recommend control intervals in screening programmes for diabetic retinopathy.

Purpose: Treatment of diabetic maculopathy with vascular endothelial growth factor inhibitors is in some patients ineffective, and, therefore, parameters predicting visual outcome after treatment should be identified. It has been shown that fixational saccades are increased in patients with reduced visual acuity secondary to diabetic maculopathy, but it is unknown to what extent these saccades in an eye affected by diabetic maculopathy are influenced by the other eye during binocular fixation. Methods: In 57 eyes from 29 diabetic patients with clinically significant macular edema, fixational eye movements were recorded using the iView X™ video-based eye tracker, and quantitative measures of fixation with the worst eye obtained during monocular and binocular fixation were compared. Results: Fixational saccades during monocular fixation had a significantly higher frequency (p = 0.005), a larger amplitude (p = 0.03), and involved a larger retinal area (p = 0.02) than during binocular fixation. There was a significant negative correlation (r2 = 0.18, p = 0.02) between visual acuity and the area of fixation during monocular but not during binocular fixation (r2 = 0.007, p = 0.68). Conclusion: Binocular fixation can reduce the area of fixation and the amplitude of fixational saccades in the worst eye of patients with diabetic maculopathy. Fixational saccades in diabetic maculopathy should be studied during monocular fixation.

In this case report, a 53-year-old female with a pathological subtrochanteric femur fracture received a cemented resection tumour prosthesis. The patient was post-operatively diagnosed with Purtscher's retinopathy due to fat embolisation. Purtscher's retinopathy has previously been described in trauma patients, however, no previous reports exist with patients treated with prosthesis. No treatment guideline is available. There is a risk of permanent visual impairment, and it is recommended, that patients presenting reduced vision post-operatively are referred to an ophthalmologist without delay for correct diagnosis.

PURPOSE: Direct ophthalmoscopy can reveal systemic, neurologic and ophthalmic conditions, but is poorly mastered among young physicians. A theoretical test is needed to measure effect of educational interventions. We developed and gathered validity evidence for a multiple-choice questionnaire (MCQ)-based theoretical test in direct ophthalmoscopy.METHODS: The MCQ was developed by interviewing experts. Then, validity evidence was evaluated using Messick's validity framework. Content was ensured by inviting the experts to contribute in a Delphi-like process. Response process was ensured by piloting and by streamlining all instructions. Then, the test was taken by ophthalmologists and by medical students without experience in direct ophthalmoscopy. Results were used to evaluate internal structure (item quality analysis and internal consistency), relations to other variables (correlation of test scores to experience level) and consequences (establishment of pass-fail score and the consequences of its use).RESULTS: The first phase of the study yielded 100 MCQs. In second phase, we identified that 60 items fulfilled predefined relevance and item quality requirements. These items demonstrated very high internal consistency (Cronbach's alpha = 0.95), significantly discriminated medical students from specialists (p < 0.001, independent samples t-test) and the established pass-fail score of 50 (83%) correct answers resulted in no false positives (students passing) and no false negatives (specialists failing). A Decision study identified that sampling 15 items suffice for certification.CONCLUSION: We developed and validated an MCQ-based theoretical test in direct ophthalmoscopy that enables an evidence-based approach to measuring, evaluating and certifying the theoretical knowledge necessary for direct ophthalmoscopy.

BackgroundThe oxygen saturation in larger retinal vessels has been shown to increase with increasing diabetic retinopathy (DR) grade and to help predict the effect of antivascular endothelial growth factor treatment in patients with diabetic maculopathy. However, it is unknown to what extent the increased oxygen saturation co-varies with other risk factors and whether it is an independent risk factor for the severity of DR.MethodsSeven hundred and twenty-two successive patients referred for specialist evaluation of diabetic retinopathy including retinal oximetry were studied. Multiple regression analysis was used to investigate whether oxygen saturation in the larger retinal arterioles and venules contributed to the severity of diabetic retinopathy, independently of gender, age, diabetes duration, diabetes type, body mass index, blood pressure, haemoglobin A1c, visual acuity and central retinal thickness.ResultsThe included parameters could explain less than 15% of the variation in retinopathy grade. Approximately, one-third of the explained variation was related to the retinal oxygen saturation.ConclusionsProspective studies are needed to evaluate whether retinal oxygen saturation is predictive for the development of diabetic retinopathy and how it interacts with other biomarkers and risk factors over time.

Background: Diabetic retinopathy is characterised by morphological lesions in the retina secondary to disturbances in retinal blood flow. Previous studies have shown that the carbonic anhydrase inhibitor (CAI) dorzolamide can induce immediate dilatation of retinal arterioles and a sustained increase in retinal blood flow in primary open-angle glaucoma. However, the effect of sustained treatment with CAI on retinal arterioles in normal persons and in patients with diabetic retinopathy is unknown. Methods: The Dynamic Vessel Analyzer was used to assess the baseline diameter and the diameter response of retinal arterioles during an increase in arterial blood pressure induced by isometric exercise and during flicker stimulation before and 2 h, 24 h and 1 week after onset of topical treatment with dorzolamide. At each examination the diameter responses were studied before and during breathing in of a hypercapnic gas mixture. Results: Treatment with dorzolamide for 1 week significantly increased the diameter of retinal arterioles in normal persons, and breathing in of a hypercapnic gas mixture reduced this response. The pathological vasodilatation and reduced retinal autoregulation in patients with diabetic retinopathy were unaffected by dorzolamide and hypercapnia. Conclusions: The study suggests a lack of relevance of CAI for the treatment of pathological vasodilatation in early diabetic retinopathy.

Retinal oximetry imaging of retinal blood vessels measures oxygen saturation of hemoglobin. The imaging technology is non-invasive and reproducible with remarkably low variability on test-retest studies and in healthy cohorts. Pathophysiological principles and novel biomarkers in several retinal diseases have been discovered, as well as possible applications for systemic and brain disease. In diabetic retinopathy, retinal venous oxygen saturation is elevated and arteriovenous difference progressively reduced in advanced stages of retinopathy compared with healthy persons. This correlates with pathophysiology of diabetic retinopathy where hypoxia stimulates VEGF production. Laser treatment and vitrectomy both improve retinal oximetry values, which correlate with clinical outcome. The oximetry biomarker may allow automatic measurement of severity of diabetic retinopathy and predict its response to treatment. Central retinal vein occlusion is characterized by retinal hypoxia, which is evident in retinal oximetry. The retinal hypoxia seen on oximetry correlates with the extent of peripheral ischemia, visual acuity and thickness of macular edema. This biomarker may help diagnose and measure severity of vein occlusion and degree of retinal ischemia. Glaucomatous retinal atrophy is associated with reduced oxygen consumption resulting in reduced arteriovenous difference and higher retinal venous saturation. The oximetry findings correlate with worse visual field, thinner nerve fiber layer and smaller optic disc rim. This provides an objective biomarker for glaucomatous damage. In retinitis pigmentosa, an association exists between advanced atrophy, worse visual field and higher retinal venous oxygen saturation, lower arteriovenous difference. This biomarker may allow measurement of severity and progression of retinitis pigmentosa and other atrophic retinal diseases. Retinal oximetry offers visible light imaging of systemic and central nervous system vessels. It senses hypoxia in cardiac and pulmonary diseases. Oximetry biomarkers have been discovered in Alzheimer's disease and multiple sclerosis and oxygen levels in the retina correspond well with brain.

Purpose: Remote ischemic conditioning (RIC) implies that transient ischemia in one organ can affect blood flow and protect from ischemia in another remote organ such as the retina. The purpose of the present study was to investigate the effect of RIC on the diameter of retinal arterioles in patients with diabetic retinopathy and whether this effect differs among peripheral and macular vessels. Methods: In twenty type 1 diabetes patients aged 20–31 years, the Dynamic Vessel Analyzer (DVA) was used to measure diameters of peripheral and macular arterioles during rest, isometric exercise, and flicker stimulation. Measurements were obtained before, immediately after, and 1 h after RIC, and were compared to responses obtained from normal persons. Results: The reduced baseline diameter (p ' 0.009) and contraction of peripheral retinal arterioles during isometric exercise (p = 0.025) observed immediately after RIC in normal persons were absent in the studied diabetic patients. Conclusions: RIC affects the diameter of peripheral but not macular arterioles in normal persons, but the response is abolished in diabetic patients. Trial registration: NCT03906383.

We investigated whether the substrate for nitric oxide (NO) production, extracellular l-arginine, contributes to relaxations induced by activating small (SKCa) conductance Ca2+-activated potassium channels. In endothelial cells, acetylcholine increased 3H-l-arginine uptake, while blocking the SKCa and the intermediate (IKCa) conductance Ca2+-activated potassium channels reduced l-arginine uptake. A blocker of the y+ transporter system, l-lysine also blocked 3H-l-arginine uptake. Immunostaining showed co-localization of endothelial NO synthase (eNOS), SKCa3, and the cationic amino acid transporter (CAT-1) protein of the y+ transporter system in the endothelium. An opener of SKCa channels, cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine (CyPPA) induced large currents in endothelial cells, and concentration-dependently relaxed porcine retinal arterioles. In the presence of l-arginine, concentration-response curves for CyPPA were leftward shifted, an effect unaltered in the presence of low sodium, but blocked by l-lysine in the retinal arterioles. Our findings suggest that SKCa channel activity regulates l-arginine uptake through the y+ transporter system, and we propose that in vasculature affected by endothelial dysfunction, l-arginine administration requires the targeting of additional mechanisms such as SKCa channels to restore endothelium-dependent vasodilatation.

The clinical presentation of the most frequent vision threatening retinal diseases is dominated by lesions indicating that disturbances in retinal blood flow are involved in the pathogenesis of these diseases. The present review describes the experience from a translational strategy pursued to investigate retinal vascular diseases with diabetic retinopathy as the main object. The normal regulation of retinal blood flow is investigated in porcine retinal vessels in vitro and ex vivo. Subsequently, the in vitro findings are translated to clinical studies in normal persons in vivo, and it is investigated whether the mechanisms are disturbed in retinal vascular disease. This is followed by clinical intervention studies on these diseases. The approach has been used to investigate pressure autoregulation, metabolic autoregulation and vasomotion in retinal vessels. The investigations have shown that retinal vascular tone can be regulated by receptor-specific agonists and antagonists to vasoactive compounds such as purines, prostaglandins and nitric oxide synthesis and that the vasoactive effects can be modulated by the concentration and the mode of administration of these compounds. Additionally, it has been shown that retinal precapillary arterioles and capillaries not visible by ophthalmoscopy may play an important role for the pathophysiology of retinal vascular disease and its treatment. Future studies should focus on investigating normal and pathological regulation of retinal blood flow in these smaller vessels.

Purpose: Diabetic retinopathy is characterized by disturbances in retinal blood flow mediated by capillary occlusion, intraretinal microvascular abnormalities (IRMAs), neovascularizations, and omega loops and reduplications. It is likely that the study of oxygen saturation in these abnormalities can provide knowledge about their role in the development of diabetic retinopathy. Methods: The oxygen saturation in IRMA vessels and venous loops and reduplications were studied in 40 diabetic patients with severe nonproliferative or proliferative diabetic retinopathy. The saturation values in the studied vascular abnormalities were compared to those of the larger retinal arterioles and venules. Results: There was a similar oxygen saturation (mean ± SD) in IRMAs observed to connect arterioles with venules (78.6% ± 11.8%, n = 22) and IRMAs connecting venules with venules (79.2% ± 9.0%, n = 12; P > 0.999). The saturation in IRMAs was significantly lower (P < 0.0002) than in arterioles (97.4% ± 5.2%, n = 40) and significantly higher (P < 0.0001) than the saturation in omega loops and reduplications (54.2% ± 19.3%, n = 6), which in turn showed no significant difference from the saturation in the venules (61.8% ± 6.8%, n = 40, P = 0.4). Conclusions: The findings suggest that the oxygen saturation in vascular abnormalities in diabetic retinopathy depends on the extent of arteriovenous (A-V) shunting, with venous saturation due to no A-V shunting in venous loops and reduplications, and intermediate oxygen saturation due to moderate shunting in IRMAs. This may precede the development of neovascularizations with arterial oxygen saturation due to high A-V shunting.

Purpose: Dual wavelength retinal oximetry allows the quantification of oxygen saturation in the larger retinal vessels. However, the technique might be refined further by identifying factors that are responsible for the different oxygen saturations in first order arterioles from the same eye shortly after their branching from the central retinal artery. The purpose of the present study is to investigate whether these factors involve rheological characteristics in the studied vessels. Materials and Methods: In fourty healthy persons the oxygen saturation was measured by dual wavelength oximetry and the blood flow by Doppler OCT in the upper and lower temporal and nasal arterioles and venules shortly after their branching from the central retinal artery and vein. The relationship of the measured oxygen saturations with age, vessel diameter, and blood linear velocity were assessed. Results: The measured oxygen saturations were (mean± SD) 97.8% ± 6.4% in the arterioles and 60.2% ± 8.8% in the venules. For both the arterioles and the venules the measured oxygen saturation (Sm) correlated significantly with the linear velocity (v) of the blood in mm/s (Sm = 101.6-0.28*v, p < 0.0001 for arterioles and Sm = 64.5-0.38*v, p = 0.002 for venules). After correction for the variation in linear velocity, the differences in saturation between first order branches from both arterioles and venules were significantly reduced and the standard deviation of the oxygen saturations were reduced to less than one third. Conclusions: Measurements of oxygen saturation in larger retinal arterioles and venules using dual wavelength oximetry can be improved by correcting for the influence of the linear velocity of the blood.

Purpose According to cross-sectional studies, oxygen saturation is elevated in retinal vessels in diabetic patients. We evaluated how retinal oxygenation (metabolic marker), vessel diameters and retinopathy grade (structural markers) change over time in diabetic patients. Design Prospective cohort study following screening in a hospital setting. Methods Retinal oximetry images were acquired in 214 patients with the Oxymap T1 oximeter. Imaging was repeated after a median of 3.0 years (range 0.76–6.8 years). Oxygen saturation and vessel diameters were measured in the right eye. Semiquantitative grading of retinopathy according to international guidelines and red lesion count were performed on fundus photographs. Results Retinopathy grade according to the international semiquantitative grading system was unchanged. Arteriolar saturation increased by 0.75±0.15 percentage points per year of follow-up (p0.44). Conclusions Oxygen saturation in larger retinal vessels can increase and arteriovenous difference can decrease over time in diabetic patients without any observable changes in retinopathy grade. The results suggest that changes in retinal oxygen saturation may precede progression of diabetic retinopathy or that oxygen saturation is more sensitive to disease progression than retinopathy grade.

BACKGROUND: Diabetic retinopathy is characterised by morphological lesions in the ocular fundus related to disturbances in retinal blood flow. The two vision threatening forms of retinopathy show specific patterns of distribution of retinal lesions with proliferative diabetic retinopathy (PDR) developing secondary to ischaemia and hypoxia in the retinal periphery and diabetic maculopathy (DM) developing secondary to hyperperfusion and increased vascular permeability in the macular area. These differences in the distribution of retinal lesions might be reflected in regional differences in oxygen saturation in the larger retinal vessels.METHODS: Dual-wavelength retinal oximetry was performed in 30 normal persons, 30 patients with DM and 30 patients with PDR, and the oxygen saturation was measured in peripapillary vessels supplying the four retinal quadrants and in branches from the upper temporal arcades supplying, respectively, the macular area and the retinal periphery.RESULTS: The overall oxygen saturation was significantly higher in diabetic patients than in normal persons and the arteriovenous (AV) saturation difference significantly lower in the patients with DM. The regional variation in oxygen saturation was similar in the three studied groups with a decreasing saturation from the upper nasal through the lower nasal, lower temporal and the upper temporal peripapillary vessels, and with a significantly higher oxygen saturation in venules draining the macular area than in venules draining the retinal periphery.CONCLUSIONS: The regional differences in retinal lesions in vision threatening diabetic retinopathy are not reflected in regional differences in the oxygen saturation of larger retinal vessels. The development of vision threatening diabetic retinopathy depends on other factors, such as, for example, regional differences in the retinal microcirculation.

PURPOSE: Retinal neovascularizations in proliferative diabetic retinopathy have been proposed to develop from larger retinal venules. However, angiographic evidence suggests that the new vessels may originate from both arterioles and venules, and the vitreous oxygen tension near retinal neovascularizations is similar to that of retinal arterioles. An assessment of the oxygen saturation in neovascularizations may help characterizing the vascular origin of these vessels in proliferative diabetic retinopathy.METHODS: Dual wavelength oximetry was used to study the oxygen saturation in arterioles, venules, and retinal neovascularizations in 40 eyes from 40 patients with proliferative diabetic retinopathy.RESULTS: The oxygen saturation was significantly lower in retinal venules than in arterioles and neovascularizations (P < 0.0001), and after a correction for the influence of vessel diameter, there was no significant difference between the oxygen saturation in retinal arterioles and neovascularizations (P = 0.71). Age at onset and duration of diabetes mellitus contributed significantly to the variation in oxygen saturation of the venules, whereas none of the clinical background parameters contributed to the variation in oxygen saturation in arterioles and neovascularizations.CONCLUSION: The oxygen saturation in retinal neovascularizations in proliferative diabetic retinopathy is similar to that of the arterioles. Neovascularizations may act as shunts to bypass areas of capillary occlusion.

Aim: Whether or not Roux-en-Y gastric bypass (RYGB) and the derived metabolic improvements are beneficial to diabetic retinopathy is controversial. We aimed to determine the presence and development of retinopathy in individuals with obesity and Type 2 diabetes treated by RYGB compared with non-operated controls, and to determine the role of diabetes remission. Methods: We graded fundus photography using the Wisconsin Epidemiologic Study of Diabetic Retinopathy in 96 individuals with obesity and Type 2 diabetes treated by RYGB 6 years after surgery compared with 48 non-operated controls. In a subsample, we investigated the development of retinopathy over time. In the secondary analysis, we divided the RYGB group according to diabetes remission. Results: RYGB surgery was not statistically associated with less retinopathy [relative risk (RR) 0.82, 95% CI 0.59 to 1.14], when adjusted for diabetes duration, sex, age and BMI. During 5.9 years of follow-up, retinopathy grading in the RYGB group was unchanged, whereas the control group displayed worse grading by 0.69 steps (95% CI 0.18 to 1.19). The RYGB group with diabetes remission (52%) showed a trend towards less retinopathy [adjusted RR (aRR) 0.45; 95% CI 0.19 to 1.06] than controls, and less retinopathy (aRR 0.33; 95% CI 0.11 to 0.94) than the RYGB group without remission in the cross-sectional data. Conclusions: In a cross-sectional setting, individuals with Type 2 diabetes treated by RYGB showed a tendency towards less retinopathy than non-operated controls, in particular diabetes remission following RYGB was associated with less retinopathy. Moreover after 5.9 years, retinopathy in the RYGB group had progressed less than in the control group. (Clinical Trial Registry No: NCT02625649).

Background: Coats’ disease is characterized by vascular hyperpermeability, oedema and accumulation of exudates related to impairment of retinal vascular function. The background for the development of the disease is unknown, but it is likely that the study of diameter changes of retinal vessels may contribute to understanding the pathophysiology of the disease. Methods: In seven patients with unilateral Coats’ disease (mean age = 34.7 years, range: 11–69 years), the baseline diameter and reactivity of retinal vessels during an increase in the arterial blood pressure by isometric exercise and in the metabolism by flicker stimulation were measured on video recordings of the retina obtained with the Dynamic Vessel Analyzer. Results: The baseline diameter of retinal vessels was larger in the affected than in the unaffected eyes which was significant for the arterioles (p = 0.02), but not for the venules (p = 0.15). During an increase in the arterial blood pressure induced by isometric exercise, the normal contraction of arterioles was absent in both eyes (p > 0.7), whereas there was a significant dilatation of the venules in the unaffected eyes (p = 0.04). Stimulation with flickering light induced normal dilatation of retinal vessels in both affected and unaffected eyes. Conclusion: Unilateral Coats’ disease is accompanied by vasodilatation in the affected eye but impaired pressure autoregulation in both eyes. A further investigation of the disease should include an elucidation of the background for dilatation of retinal vessels in affected eyes and whether impaired pressure autoregulation can be found in vessels elsewhere in the body.

The purpose is to use laws of physics to elucidate the mechanisms behind capillary non-perfusion in diabetic retinopathy. In diabetic retinopathy, loss of pericytes weakens capillary walls and the vessel dilates. A dilated capillary has reduced resistance to flow, therefore increased flow in that vessel and decreased in adjoining capillaries. A preferential shunt vessel is thus formed from the dilated capillary and the adjacent capillaries become non-perfused. We apply the laws of Laplace and Hagen-Poiseuille to better understand the phenomena that lead to capillary non-perfusion. These laws of physics can give a foundation for physical or mathematical models to further elucidate this field of study. The law of Laplace predicts that a weaker vessel wall will dilate, assuming constant transmural pressure. The Hagen-Poiseuille equation for flow and the Ostwald-de Waele relationship for viscosity predict that a dilated vessel will receive a higher portion of the fluid flow than the adjoining capillaries. Viscosity will decrease in the dilated vessel, furthering the imbalance and resulting in a patch of non-perfused capillaries next to the dilated 'preferential' shunt vessel. Physical principles support or inspire novel hypotheses to explain poorly understood phenomena in ophthalmology. This thesis of pericyte death and capillary remodelling, which was first proposed by Cogan and Kuwabara, already agrees with histological and angiographical observations in diabetic retinopathy. We have shown that it is also supported by classical laws of physics.

PURPOSE: The epidemiology, risk factors, and the effect of anti-VEGF treatment on neovascular age-related macular degeneration (nAMD) have primarily been studied in the first eye developing the disease. The understanding of pathophysiology and planning of follow-up examinations can be improved by knowledge of incidence and risk factors for development of the disease in the fellow eye.METHODS: In a prospective observational cohort study, epidemiological and clinical risk factors for the development of nAMD in the fellow eye among 2516 patients consecutively diagnosed with the disease from a population of 0.9 million citizens during a period of more than 10 years were studied.RESULTS: nAMD had been diagnosed in the fellow eye of 541 (21.5%) of the patients. The incidence of fellow-eye involvement increased from approximately 5% in patients initially presenting with bilateral disease to approximately 28% more than 6 years after the diagnosis in the first eye. Visual acuity (VA) was higher and central retinal thickness (CRT) was lower in fellow eyes with nAMD diagnosed later than the first eye. Male gender, increasing leakage area, and peripapillary location of the subretinal neovascular membrane in the first eye reduced the risk of developing disease in the fellow eye.CONCLUSIONS: The planning of follow-up examinations of patients diagnosed with nAMD in one eye should consider that the risk of fellow-eye involvement is higher within the first 6 years, in women, and when the leakage area in the first eye is small and not located peripapillary.

MicroRNAs (miRNAs) are key regulators of gene expression in humans. Overexpression or depletion of individual miRNAs is associated with human disease. Current knowledge suggests that the retina is influenced by miRNAs and that dysregulation of miRNAs as well as alterations in components of the miRNA biogenesis machinery are involved in retinal diseases, including age-related macular degeneration (AMD). Furthermore, recent studies have indicated that the vitreous has a specific panel of circulating miRNAs and that this panel varies according to the specific pathological stress experienced by the retinal cells. MicroRNA (miRNA) profiling indicates subtype-specific miRNA profiles for late-stage AMD highlighting the importance of proper miRNA regulation in AMD. This review will describe the function of important miRNAs involved in inflammation, oxidative stress and pathological neovascularization, the key molecular mechanisms leading to AMD, and focus on dysregulated miRNAs as potential therapeutic targets in AMD.

Objectives Steroid treatment can accelerate visual recovery in patients with optic neuritis (ON), but it is unknown whether the timing of the start of treatment influences the outcome. The main purpose of this observational study was to assess the effect of early onset steroid treatment of ON on visual prognosis and retinal morphology. Methods Forty‐nine patients with acute mild/moderate (n = 21) or severe (n = 28) ON, and an equal number of healthy controls were enrolled. Patients with severe ON either received early onset steroid treatment (initiated within 1 week of presentation with visual loss) (n = 9), late‐onset treatment (initiated after 1 week) (n = 13), or no treatment (n = 6). Visual function and retinal morphology was studied after 6 and 12 months. Results All measures of visual function had improved after 6 months (p ≤ 0.03) in the three groups with severe ON. This was not the case for Rayleigh match setting range (SR) in the nontreated group (p = 0.24), or for SR (p = 0.08) and latency to P100 of visual evoked potential (p = 0.08) in the late‐onset treated group. After 12 months, further improvement occurred in the nontreated and late‐treated groups, but not in the early treated group. Macular retinal nerve fiber layer (mRNFL) and ganglion cell plus inner plexiform layer had decreased significantly (p ≤ 0.001) in all three groups with severe ON after 6 months. After 12 months, only mRNFL had further significantly decreased and only in the late‐onset treated group (p = 0.02). Conclusion The beneficial effects of early onset steroid treatment of ON is limited to a few months whereas the long‐term prognosis is independent of the timing of treatment.

For many years, it is not fully understood how non-drainage scleral buckling surgery brings about spontaneous reattachment of the detached retina when retinal breaks remain open at the end of surgery. Various explanations have been put forward, but none more interesting than the effect of fluid currents associated with eye movements. One such explanation involved the physics of the Bernoulli's principle. Daniel Bernoulli was an eighteenth century Swiss mathematician and he described an equation based on the conservation of energy. The sum of pressure energy, potential energy and kinetic energy remains constant. Bernoulli's equation usually applies to closed system such as the flow of fluid through pipes. When fluid flows through a constriction, the speed of fluid increases, the kinetic energy increases. If there was no change in elevation (potential energy), then the increase in kinetic energy must be accompanied by a decrease in pressure energy. In ophthalmic surgery, the Bernoulli's effect is the basis for venturi pumps that drive vitrectomy and phacoemulsification machines. This essay expounds on how Bernoulli's effect might be relevant to scleral buckling for retinal detachment repair. In the era when vitrectomy is increasing the primary surgical operation for retinal detachment, the pervasive advice is to emphasise the importance of patient adopting head posture and remaining still postoperatively. The exception is non-drainage scleral buckling surgery. Early postoperative mobilisation may be vital to achieve reattachment.

Purpose: Remote ischemic conditioning (RIC) implies that transient ischemia in a limb can affect perfusion in a target organ elsewhere in the body. The changes in perfusion can be assumed to be paralleled by changes in the vessel diameters in the target organ. It remains to be elucidated whether the diameter of normal retinal vessels can be used as a marker of RIC in vivo.Methods: In 20 normal persons aged 20 to 31 years the Dynamic Vessel Analyzer (DVA) was used to measure the resting diameter and diameter changes during isometric exercise and flicker stimulation before, immediately after, and 1 hour after RIC induced by transient ischemia in the left arm.Results: The baseline diameter of retinal venules was reduced nonsignificantly immediately after (P = 0.07) and significantly 1 hour after RIC (P = 0.009), whereas the baseline diameter of arterioles was unaffected by the intervention (P = 0.61). Arterial constriction induced by isometric exercise was significantly reduced immediately after RIC (P = 0.04), but not 1 hour after RIC (P = 0.99). None of the other diameter responses were affected by RIC (P = 0.22 for all comparisons).Conclusions: The diameter of retinal vessels might potentially be a marker of ischemic conditioning in the body in general. The effect of RIC on retinal vascular diseases where ischemia is a part of the pathogenesis should be investigated.

Occlusion of retinal vessels leads to retinal ischaemia and hypoxia, which induces vasodilatation in adjacent retinal areas in order to normalize retinal oxygenation. Previous studies have shown that NO and COX products are involved in hypoxia-induced dilatation of retinal arterioles in vitro and in vivo, and that this response is disturbed in patients with diabetes mellitus. However, it is unknown to what extent post-hypoxic recovery of the diameter of retinal arterioles depends on NO and COX products in normal persons and in diabetic patients. The Dynamic Vessel Analyzer (DVA) was used to study the post-hypoxic diameter changes of larger retinal vessels in 20 normal persons, 20 diabetic patients without diabetic retinopathy, and in 18 patients with diabetic maculopathy before and after inhibition of the synthesis of nitric oxide and COX products. In normal persons, the arterioles had re-constricted (p > 0.99) 2 minutes after termination of hypoxia in the absence of antagonists, but not after treatment with L-NMMA and diclofenac (p < 0.01 for all comparisons). In diabetic patients without retinopathy, the arterioles showed no diameter changes after termination of hypoxia during any of the interventions. In patients with diabetic maculopathy hypoxia had not dilated retinal arterioles (p > 0.1 for all comparisons) to allow the study of re-constriction. In all groups, the dilatation of venules remained significantly increased during the post-hypoxic observation period, both in the absence and in the presence of L-NMMA and diclofenac.Post-hypoxic constriction of retinal arterioles depends on NO and COX products, and is impaired in diabetic patients before the development of retinopathy. This disturbance may contribute to the development of diabetic retinopathy, and should be the target of future interventional studies aimed at preventing and treating the disease.ClinicalTrials.gov identifier: NCT01689090.