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Competing Interests: Competing interests: None declared.

Background: To investigate whether neonatal hyperglycaemia in the first postnatal week is associated with treatment-demanding retinopathy of prematurity (ROP)., Methods: This is a Danish national, retrospective, case-control study of premature infants (birth period 2003-2006). Three national registers were searched, and data were linked through a unique civil registration number. The study sample consisted of 106 cases each matched with two comparison infants. Matching criteria were gestational age (GA) at birth, ROP not registered and born at the same neonatal intensive care unit. Potential 'new' risk factors were analysed in a multivariate logistic regression model, while adjusted for previously recognised risk factors (ie, GA at birth, small for gestational age, multiple birth and male sex)., Results: Hospital records of 310 preterm infants (106 treated; 204 comparison infants) were available. Nutrition in terms of energy (kcal/kg/week) and protein (g/kg/week) given to the preterm infants during the first postnatal week were statistically insignificant between the study groups (Mann-Whitney U test; p=0.165/p=0.163). Early postnatal weight gain between the two study groups was borderline significant (t-test; p=0.047). Hyperglycaemic events (indexed value) were statistically significantly different between the two study groups (Mann-Whitney U test; p<0.001). Hyperglycaemia was a statistically independent risk factor (OR: 1.022; 95% CI 1.002 to 1.042; p=0.031)., Conclusion: An independent association was found between the occurrence of hyperglycaemic events during the first postnatal week and later development of treatment-demanding ROP, when adjusted for known risk factors., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background/aims: To compare the visual outcome in early versus deferred surgery in patients with idiopathic epiretinal membrane (ERM) and good presenting visual acuity and mild symptoms., Methods: This study is a randomised clinical trial. 53 eyes of 53 patients with symptomatic ERM and best-corrected visual acuity (BCVA) at presentation ≥65 early treatment diabetic retinopathy study (ETDRS) letters were randomised to immediate surgery (20 eyes) or to watchful waiting (33 eyes) for 1 year. Primary end-point was BCVA after 12 months. Secondary end-points were central macular thickness and the number of patients that crossed over from the watchful waiting arm to the surgery arm due to deteriorated symptoms., Results: Mean BCVA after 12 months in the watchful waiting group (81 letters) were not significantly different from patients undergoing immediate surgery (82.5 letters, p=0.647). During 1 year of follow-up, eight patients in the watchful waiting group (24%) crossed over to surgery and these patients gained a mean of 3.1 letters (SEM 1.38). Patients randomised to immediate surgery gained approximately one line. Watchful waiting patients who remained without surgery were stable. The visual acuity gain after surgery is slow and gradual until 9 months postoperatively. There were no serious complications such as retinal detachment or infectious endophthalmitis., Conclusions: Vitrectomy for early symptomatic ERM is beneficial in preserving excellent vision. A watchful waiting approach with 1 year of follow-up is safe in the sense that this group does not lose five ETDRS letters in waiting. Deferral of surgery by regular monitoring of patients is a safe approach., Trial Registration Numbers: H-C-2008-026 and NCT00902629., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Purpose: To examine non-mydriatic fundus photography (FP) and fundus autofluorescence (FAF) as alternative non-invasive imaging modalities to fluorescein angiography (FA) in the detection of cuticular drusen (CD)., Methods: Among 2953 adults from the Danish Rural Eye Study (DRES) with gradable FP, three study groups were selected: (1) All those with suspected CD without age-related macular degeneration (AMD) on FP, (2) all those with suspected CD with AMD on FP and (3) a randomly selected group with early AMD. Groups 1, 2 and 3 underwent FA and FAF and group 4 underwent FAF only as part of DRES CD substudy. Main outcome measures included percentage of correct positive and correct negative diagnoses, Cohen's κ and prevalence-adjusted and bias-adjusted κ (PABAK) coefficients of test and grader reliability., Results: CD was correctly identified on FP 88.9% of the time and correctly identified as not being present 83.3% of the time. CD was correctly identified on FAF 62.0% of the time and correctly identified as not being present 100.0% of the time. Compared with FA, FP has a PABAK of 0.75 (0.60 to 1.5) and FAF a PABAK of 0.44 (0.23 to 0.95)., Conclusions: FP is a promising, non-invasive substitute for FA in the diagnosis of CD. FAF was less reliable than FP to detect CD., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Aim: To evaluate the full thickness macular hole (FTMH) closure rate in patients positioning non-supine (NSP) compared with patients positioning face-down (FDP)., Methods: We retrospectively reviewed two FTMH case series-postoperative positioning was FDP and NSP, respectively. All eyes were pseudophakic and treatment consisted of pars plana vitrectomy, internal limiting membrane peeling and perfluoropropane gas tamponade. Primary outcome measure was FTMH closure verified by optical coherence tomography. Secondary outcome was ETDRS visual acuity 6 months postoperatively., Results: Over 13.7 months 122 eyes were included in this study, 66 eyes in the FDP group and 56 eyes in the NSP group. Closure rates were 95.5% and 96.4% in the FDP group and the NSP group, respectively. Median postoperative visual acuity at 6 months was 69 ETDRS letters in both positioning groups (p=0.64). Neither positioning group fully complied with the recommended positioning protocol., Conclusions: Results from consistent FTMH repair indicate similar anatomical success rates in FDP and NSP groups, suggesting that FDP is unnecessary. Objective monitoring of positioning would be beneficial in future FTMH studies to be able to adjust for positioning protocol compliance., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Aims: Quantitative assessment of the rate of progression of recent onset posterior rhegmatogenous retinal detachment (RRD)., Methods: A prospective observational study on patients presenting with acute symptomatic primary foveola-on RRD over a 32-month period. Patients were evaluated with optical coherence tomography (OCT) to confirm foveola status. A total of 96 eyes were enrolled and 50 were eligible for quantitative measurement of the movement of the detachment by OCT., Results: Only one eye progressed from foveola-on to foveola-off in the 96 evaluated eyes. In seven of the 50 eyes eligible for quantitative measurement, the detachment was stable during admission. In all others, the movement was very dynamic with episodes of progression and regression. We found that 18% (9/50) of the detachments had a net movement towards foveola during admission. Logistic regression established the amount of time admitted (OR=1.05, p=0.027) as significant risk factor for progression., Conclusions: The risk of progression of a foveola-on RRD to affect the fovea is small the first night of admission (1%). The amount of time surgery is delayed was found as significant risk factor for progression towards foveola., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Purpose: To investigate the effect of intravitreal injections of the vascular endothelial growth factor inhibitor ranibizumab on retinal oxygenation in patients with central retinal vein occlusion (CRVO)., Methods: Retinal oxygen saturation in patients with CRVO was analysed using the Oxymap Retinal Oximeter P3, before and during 6 months of treatment with intravitreal injections of ranibizumab., Results: At presentation, retinal venous oxygen saturation was lower in eyes with CRVO than in the healthy fellow eyes (32±13% vs 59±10%, respectively, p=0.001) whereas retinal arterial saturation was higher in eyes with CRVO than in the fellow eyes (95%±8% and 91%±3%, p=0.04). Mean visual acuity increased from 51±24 letters ETDRS at baseline to 66±24 and 69±20 letters ETRDS, respectively, at 3 months and 6 months treatment (mean±SD, p<0.0001, repeated measures analysis of variance) and central retinal thickness was reduced from 697±139 µm to 368±113 µm and 340±96 µm, respectively, from baseline to 3 months and 6 months treatment (p<0.0001). Venous saturation increased during treatment (from 35.5%±13.8% at baseline to 43.1%±10.8% and 43.5%±13.7% after 3 months and 6 months treatment, respectively, p=0.012), while no significant change was found in arterial saturation (p=0.24)., Conclusions: Retinal venous oxygen saturation was markedly reduced in untreated CRVO and was roughly halfway normalised during intravitreal ranibizumab treatment. Retinal artery oxygen saturation was not reduced in CRVO., Trial Registration Number: NCT01360385., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objectives: To investigate inter-reader agreement on five severity levels of central vascular changes (none, mild, moderate, severe pre-plus disease, plus disease) and aggressive posterior retinopathy of prematurity (ROP), and to see whether an unintended shift in indication for treatment occurred., Methods: Four international ROP readers participated. Before the grading of the photographs, the readers were informed that a high proportion of advanced ROP cases were included. In total, 243 photographs/948 quadrants were available from 136 infants. As a standard series of photographs was available, grading was performed under optimised conditions., Results: The four readers agreed on the quadrant scores of only 70 (7.38%) of the 948 quadrants--that is, on 1, 5, 15, 4 and 45 quadrants for scores 0, 1, 2, 3 and 4, respectively. The mean scores differed systematically between the readers (permutation test, p<0.0001). Agreement on presence of aggressive posterior ROP from all four readers was not obtained for any of the photographs. Readers scored plus disease in at least two quadrants in 95.5% of the eyes for which treatment was indicated. All four readers agreed on the scoring of indication for treatment for 195 eyes (80.2%); however, treatment was only recommended in 18 (7.4%) eyes. One reader was found to differ systematically from the others in indicating treatment (Rasch analysis; p=0.0001). Finally, a significant shift in indication for treatment occurred between birth period 2000-2002 and 2003-2006 (Mann-Whitney rank sum test, p<0.001)., Conclusions: Inter-reader agreement on central vascular changes is poor, especially when based on more than two rating categories. The subjective nature of diagnosing such vascular changes possibly resulted in earlier treatment of preterm infants in Denmark over the entire study period (1997-2006). The recent increased incidence of treated infants in Denmark is, at least in part, explained by a significant shift in indication for treatment.

Aim: To examine postoperative macular morphology and visual outcome after 12 months in relation to internal limiting membrane (ILM) peeling versus no peeling, indocyanine green (ICG) staining and re-operation in eyes that achieved macular hole closure after surgery., Methods: Seventy-four eyes with closed stage 2 or 3 macular holes were recruited from a randomised clinical trial comparing: (1) vitrectomy without ILM peeling; (2) vitrectomy with 0.05% isotonic ICG-assisted ILM peeling; and (3) vitrectomy with 0.15% trypan blue-assisted ILM peeling. Contrast-enhanced Stratus optical coherence tomography was used to assess central foveal thickness, central photoreceptor layer thickness (CPRT), central photoreceptor layer discontinuity (PRD) and relative reflectivity of the outer nuclear layer. Outcomes were correlated with best corrected visual acuity (BCVA) 12 months after surgery., Results: BCVA was correlated with CPRT and PRD. Regression analysis and receiver operating characteristics curve analysis showed that CPRT >33 microm (OR 12.5) and PRD <177 microm (OR 9.86) were highly predictive for regaining reading vision (> or =69 Early Treatment of Diabetic Retinopathy Study letters) 12 months after surgery. No significant difference was found in postoperative macular morphology between subgroups., Conclusions: Poor vision after 12 months despite macular hole closure was associated with attenuation and disruption of the foveolar photoreceptor matrix. The extent of attenuation and disruption was independent of peeling and staining., Trial Registration Number: NCT00302328.

Aim: To determine the effect of internal limiting membrane (ILM) peeling on anatomical and functional success rates in stage 2 and 3 idiopathic macular hole surgery (MHS)., Methods: Randomised clinical trial of stage 2 and 3 idiopathic macular hole without visible epiretinal fibrosis and with less than 1 year's duration of symptoms. Eyes were randomised to (1) vitrectomy alone without retinal surface manipulation, (2) vitrectomy plus 0.05% isotonic Indocyanine Green (ICG)-assisted ILM peeling or (3) vitrectomy plus 0.15% Trypan Blue (TB)-assisted ILM peeling. Main outcomes were hole closure after 3 and 12 months and best-corrected visual acuity after 12 months., Results: 78 eyes were enrolled. Primary closure rates were significantly higher with ILM peeling than without peeling for both stage 2 holes (ICG peeling 100%, non-peeling 55%, p = 0.014) and for stage 3 holes (ICG peeling 91%, TB peeling 89%, non-peeling 36%, p<0.001). Visual outcomes in eyes with primary hole closure were not significantly different between the groups., Conclusions: Dye-assisted ILM peeling was associated with significantly higher closure rates than non-peeling in both stage 2 and 3 MHS. Intraoperative ILM staining with 0.05% isotonic ICG was not associated with a significantly different visual outcome than non-peeling or TB peeling in eyes with primary hole closure., Trial Registration Number: NCT00302328.

Aim: To present normative data of outer photoreceptor layer thickness obtained by a new semiautomatic image analysis algorithm operating on contrast-enhanced optical coherence tomography (OCT) images., Methods: Eight Stratus OCT3 scans from identical retinal locations from 25 normal eyes were registered and combined to form a contrast-enhanced average image. Utilising the vertical intensity gradients of the enhanced OCT images to demarcate retinal layers, thickness measurements of the outer photoreceptor- and retinal pigment epithelium layer (RPE-OS(complex)) were obtained. Additionally backscattered light within the outer nuclear layer (ONL) in the fovea was registered and compared with backscattered light within the ONL in the peripheral part of the macula (I(ratio)-ONL)., Results: The mean RPE-OS(complex) thickness in the foveal centre was 77.2 microm (SD = 3.95). The RPE-OS(complex) thickness in the superior macula 0.5-3 mm of the centre was significantly increased as compared with the corresponding inferior retina. In healthy subjects, the I(ratio)-ONL was 1.06., Conclusions: Contrast-enhanced OCT images enable quantification of outer photoreceptor layer thickness, and normative values may help understanding better the relationship between functional outcome and photoreceptor morphology in retinal diseases.

Aims: We investigated the effect of several Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), on the preoptic nerve oxygen tension (ONPO2), as indomethacin previously has demonstrated a strong decreasing effect on ONPO2. We tested whether these NSAIDs, like indomethacin, also reduce the increasing effect of dorzolamide on ONPO2., Methods: ONPO2 was measured 0.5 mm above the optic disc in 23 domestic pigs (26-36 kg) with a polarographic oxygen-sensitive electrode. One of the following NSAIDs was administered intravenously as increasing doses or as one large dose: indomethacin, ibuprofen, diclofenac, ketoprofen, parecyclo-oxygenase-2 inhibitor and lornoxicam. Indomethacin was both tested alone and after preceding administration of the other NSAIDs. Dorzolamide was also tested after preceding administration of NSAIDs different from indomethacin., Results: Indomethacin decreased ONPO2 significantly in a dose-dependent manner. None of the other NSAIDs produced any effect on the ONPO2 (p>>0.05; n = 17). No difference was found between the effect of indomethacin injected alone, and after preceding administration of the other NSAIDs. Intravenous dorzolamide (500 mg) increased ONPO2 by 32 (7)% (n = 7; p<0.001) after preceding administration of several NSAIDs different from indomethacin., Conclusions: Indomethacin decreased ONPO2, while the other NSAIDs showed no effect on ONPO2, and they did not affect the effect of indomethacin. The hypoxic effect of indomethacin must be due to another mechanism than cyclo-oxygenase inhibition. The effect of dorzolamide on ONPO2 is not related to prostaglandin production.

Background/aims: Prostaglandins are important in blood flow regulation. Carbon dioxide (CO(2)) breathing and carbonic anhydrase inhibition increase the oxygen tension in the retina and optic nerve. To study the mechanism of this effect and the role of cyclo-oxygenase in the regulation of optic nerve oxygen tension (ONPO(2)), the authors investigated how indomethacin affects ONPO(2) and the ONPO(2) increases caused by CO(2) breathing and carbonic anhydrase inhibition in the pig., Methods: Optic nerve oxygen tension was measured in 11 pigs with a polarographic oxygen electrode. The tip of the electrode was placed 0.5 mm above the optic disc. The effects of indomethacin, CO(2) breathing (3%) before and after indomethacin treatment, and carbonic anhydrase inhibition with or without indomethacin treatment were investigated., Results: Administration of 300 mg indomethacin decreased optic nerve oxygen tension significantly. Carbonic anhydrase inhibition and CO(2) breathing increased ONPO(2) significantly. After indomethacin had been given, the rise in ONPO(2) caused by CO(2) breathing and carbonic anhydrase inhibition was significantly reduced., Conclusion: Systemic administration of indomethacin decreases the optic nerve oxygen tension; this is probably the result of decreased blood flow through vasoconstriction of vessels in the optic nerve. Additionally, indomethacin diminishes the ONPO(2) increasing effect of CO(2) breathing and carbonic anhydrase inhibition, thus affecting the reactivity of vessels in the optic nerve.

Background/aims: The authors have previously reported that carbonic anhydrase inhibitors such as acetazolamide and dorzolamide raise optic nerve oxygen tension (ONPO(2)) in pigs. The purpose of the present study was to investigate whether timolol, which belongs to another group of glaucoma drugs called beta blockers, has a similar effect. In addition, the effect of dorzolamide and timolol in combination was studied., Methods: Polarographic oxygen electrodes were placed transvitreally over the optic disc in anaesthetised pigs and ONPO(2) was recorded continually. Drugs were administered intravenously either as 100 mg timolol followed by 500 mg dorzolamide (n = 5), 500 mg dorzolamide followed by 100 mg timolol (n = 5), or 100 mg timolol and 500 mg dorzolamide given simultaneously (n = 5). Arterial blood pressure, blood gasses, and heart rate were recorded., Results: ONPO(2) was unaffected by administration of 100 mg timolol as an intravenous injection (n = 5). Administration of 500 mg dorzolamide by itself significantly increased ONPO(2) from 2.96 (SD 0.62) kPa to 3.69 (SD 0.88) kPa (n = 4, p = 0.035). The dorzolamide induced ONPO(2) increase was not significantly different from the ONPO(2) increases were seen when dorzolamide was administered simultaneous with (n = 5) or 35 minutes (n = 5) after 100 mg timolol., Conclusion: Systemic administration of timolol does not affect the optic nerve oxygen tension despite its lowering effect on the intraocular pressure. Additionally, timolol does not affect the ONPO(2) increasing effect of dorzolamide.

Aim: To investigate the influence of acute changes in intraocular pressure on the oxygen tension in the vicinity of the optic nerve head under control conditions and after intravenous administration of 500 mg of the carbonic anhydrase inhibitor dorzolamide., Methods: Domestic pigs were used as experimental animals. Oxygen tension was measured by means of a polarographic electrode in the vitreous 0.5 mm anterior to the optic disc. This entity is called the optic nerve oxygen tension. Intraocular pressure was controlled by a hypodermic needle inserted into the anterior chamber and connected to a saline reservoir., Results: When the intraocular pressure was clamped at 20 cm H2O optic nerve oxygen tension was 20 (5) mm Hg (n=8). Intravenous administration of dorzolamide caused an increase in optic nerve oxygen tension of 43 (8)% (n=6). Both before and after administration of dorzolamide optic nerve oxygen tension was unaffected by changes in intraocular pressure, as long as this pressure remained below 60 cm H2O. At intraocular pressures of 60 cm H(2)O and below, dorzolamide significantly increased optic nerve oxygen tension., Conclusion: Intravenous administration of 500 mg dorzolamide increases the oxygen tension at the optic nerve head during acute increases in intraocular pressure.