Long-term functional and structural outcomes in patients with primary congenital glaucoma-A Danish nationwide study.

PURPOSE: Evaluation of long-term functional and structural outcomes in patients with primary congenital glaucoma (PCG) based on visual acuity (VA), visual field (VF) using standard automated perimetry, and peripapillary retinal nerve fibre layer thickness (pRNFL). METHODS: We retrospectively reviewed medical records of all patients diagnosed with PCG in Denmark from 1977 to 2016. Severe vision loss was defined as VA <6/60 and/or VF >20 decibels (dB). Prognostic factors were evaluated in a correlation matrix. RESULTS: The median age of the 94 patients (153 PCG eyes) was 12 years (IQR 9-16). In PCG eyes 62% had VA ≥6/18 but 22% had <6/60. VA in the better seeing eye was ≥6/18 in 90% and <6/60 in 5%. VF was measured in 59 PCG eyes and the median mean defect was 5.1 dB (IQR 2.1-9.6) with 52% better than 6 dB and 9% worse than 20 dB. Generalized pRNFL was reduced below the age-expected 1st percentile in 29% of the 58 PCG eyes where pRNFL was measured. Poor VA, poor VF and reduced pRNFL were all correlated (p = 0.0001). More surgeries (p < 0.0001) and longer diagnostic delay (p = 0.004) were associated with poorer vision and to a lesser degree with poor VF pRNFL. CONCLUSION: In Denmark, most patients with bilateral PCG retain VA ≥6/18 in the better seeing eye. Poor VA was associated with poor VF. Longer diagnostic delay and more surgeries were associated with a poorer prognosis.

Association between structural and functional treatment outcomes in neovascular age-related macular degeneration.

PURPOSE: The administration frequency of intravitreal anti-vascular endothelial growth factor (anti-VEGF) in neovascular age-related macular degeneration (AMD) have been widely discussed. The primary objective of the study was to explore the association between anatomical outcomes and changes in functional outcome. METHODS: This was a retrospective cohort study of patients with newly diagnosed neovascular AMD with a minimum of 12 months of follow-up. Only one eye per patient was included. Patients were treated according to the observe-and-plan or the pro-re-nata regimen. All patients were regularly examined from the time of diagnosis up to 24 months. The effect of intraretinal fluid (IRF), subretinal fluid (SRF) and pigment epithelium detachment (PED) at any time point on visual acuity (VA) was tested, as well as the long-term effect and the risk of losing VA. Further, the variability of central retinal thickness (CRT) was calculated for each eyes' individual measures during the observation period, excluding the monthly loading phase. The prognostic effect of each factor on VA was estimated by regression analysis. The primary outcome measure was VA, which was correlated with the presence or absence of fluid, seen as IRF, SRF or PED. RESULTS: A total of 504 treatment naïve eyes from 504 patients was included. The presence of IRF was associated with lower VA at all visits (p < 0.001). However, the presence of SRF or PED was not significantly associated with worse VA at any time point during the observation period. Patients in the upper quartile of CRT variance had a greater loss in VA after 12 and 24 months (p < 0.001). CONCLUSIONS: In this retrospective cohort study, the presence of intraretinal fluid was associated with poorer visual outcome in neovascular AMD patients treated with anti-VEGF, but the presence of subretinal fluid and PEDs was not. This suggests that IRF is worse than subretinal fluid and PEDs for AMD outcomes and therefore requires the most intensive treatment. Further, we found that patients with the highest CRT variability during the study period had poorer visual outcomes after 12 and 24 months, indicating that stringent control of retinal fluid volume fluctuations is important to prevent visual acuity decline over time.

[Non-invasive treatment of open-angle glaucoma].

This review provides an update on open-angle glaucoma with a special focus on the current non-invasive treatment modalities, side effects and interactions to topical pressure-lowering eye drops that all treatment providers should be aware of. We highlight current challenges in terms of timely diagnosis and compliance and outline promising areas of research within the field.

Driving vision in patients with neovascular AMD in anti-VEGF treatment.

PURPOSE: To report real-world experiences on driving vision in patients with neovascular age-related macular degeneration (AMD) undergoing intravitreal anti-VEGF treatment. METHODS: Retrospective cohort study of treatment-naïve patients with neovascular AMD commenced in anti-VEGF treatment (n = 416) and followed for 4 years in a pro re nata treatment regimen. Monocular best-corrected visual acuity (BCVA) measured using ETDRS was performed on the treatment eye at all visits and on the fellow eye at baseline, every 6 months, and upon any patient-reported change in vision. Driving vision was defined as BCVA in the best-seeing eye of ≥70 ETDRS letters (equivalent to ≥0.5 Snellen) corresponding to the minimum BCVA required in many countries. RESULTS: Driving vision was present in 280 patients (67%) and was sustained in 86%, 74%, 65% and 59% of the patients at 1, 2, 3 and 4 years, respectively. Lower BCVA in the best-seeing eye predicted loss of driving vision. In patients without driving vision at baseline, driving vision was regained in 29%, 36%, 39% and 41% of the patients at 1, 2, 3 and 4 years, respectively; but only 35% sustained driving vision after the first year. Lower age and higher BCVA in best-seeing eye predicted regain of driving vision. CONCLUSION: Driving vision can be sustained in the majority of the patients if they have driving vision at baseline. This study provides important prognostic information for patients with neovascular AMD.

Real-world 10-year experiences with intravitreal treatment with ranibizumab and aflibercept for neovascular age-related macular degeneration.

PURPOSE: To report 10-year, real-world experiences with intravitreal therapy (IVT) using vascular endothelial growth factor inhibitors for neovascular age-related macular degeneration (nAMD). METHODS: Retrospective single-centre review of IVT-log 2007-2019 with a treatment-as-needed regimen and ETDRS visual acuity charts. RESULTS: The 4,678 treatment-naïve eyes of 3,668 patients received a mean of 5.4 IVT in the first year and 4.0-4.3 IVT yearly thereafter. Baseline mean best corrected visual acuity (BCVA) was 57.9 (±16.4) letters (6/18) that improved a mean +2.1 (±0.2) letters at the first follow-up visit and gradually declined to -5.0 (±2.2) letters after 10 years. At baseline, there were 29% with BCVA ≥6/12. This proportion increased to 31-37% until year 9. There were 8% with BCVA loss of ≥3 lines at the first follow-up visit increasing to 34% after 10 years. Poorer baseline BCVA was associated with larger increase in BCVA (p < 0.0001, multiple linear regression). The 2,566 (55%) discontinued eyes had a mean baseline BCVA of 56.9 (±16.4) letters compared with 61.5 (±15.9) letters for eyes remaining in treatment. In year 0-7, the discontinued eyes lost an additional mean 2-4 letters (last observation carried forward) but were similar thereafter. There were 12.6% (74 of 585 eligible eyes) that were still in treatment after 10 years. At baseline, 10% had bilateral nAMD. Of patients with unilateral presentation, 17% had received fellow-eye IVT after 5 years. CONCLUSION: A treatment-as-needed regimen stabilized BCVA in active nAMD up to 10 years in most eyes. Baseline BCVA was the most important prognostic factor.

LOW ENDOPHTHALMITIS RATES AFTER INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR INJECTIONS IN AN OPERATION ROOM: A Retrospective Multicenter Study.

PURPOSE: To evaluate the rate of presumed endophthalmitis (EO) after intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections in three European hospitals performed in an operation room (OR) under sterile conditions. METHODS: A retrospective multicenter study between 2003 and 2016 at three European sites, City Hospital Triemli Zurich, Switzerland (CHT), Zealand University Hospital Roskilde, Denmark (ZUH) and University Clinic Bern, Switzerland (UCB). Intravitreal injection (IVI) database of each department was reviewed. All anti-vascular endothelial growth factor injections were performed using a standardized sterile technique in an operation room. Injection protocols were similar between the three sites. No preinjection antibiotics were given. Postoperative antibiotics varied among sites. RESULTS: A total of 134,701 intravitreal injections were performed at the 3 sites between 2003 and 2016. Ten cases of presumed endophthalmitis were documented: 4 in 50,721 at CHT (95% CI: 0.0071-0.0087%), 2 in 44,666 at ZUH (95% CI: 0.0039-0.0051%), and 4 in 39,314 at UCB (95% CI: 0.0092-0.011%). This results in one case in 13,470 intravitreal injections and a combined incidence of 0.0074% per injection (95% CI: 0.0070-0.0078%). Positive cultures were found in 4 out of 10 presumed endophthalmitis cases. CONCLUSION: The standardized sterile technique in an operation room with laminar airflow showed very low rates of endophthalmitis at three European sites.

Intravitreal ranibizumab for diabetic macular oedema in previously vitrectomized eyes.

PURPOSE: There is little information about the efficacy of intravitreal vascular endothelial growth factor (VEGF) inhibition in vitrectomized eyes. This study aimed to evaluate the efficacy of anti-VEGF (ranibizumab) on diabetic macular oedema in previously vitrectomized eyes. METHODS: A nationwide retrospective review of medical records from 2010 to 2013. RESULTS: We identified 33 previously vitrectomized eyes in 28 patients treated with ranibizumab injections for diabetic macular oedema. Median follow-up was 323 days (interquartile range 72-1404 days). Baseline mean visual acuity was 0.57 logMAR (95% CI 0.13-1.01) before injections. After an average of 4.7 injections (range 1-15), mean visual acuity remained stable at 0.54 logMAR (95% CI 0.13-0.95) with a mean improvement of 0.03 (p = 0. 45, 95% CI -0.12 to 0.06). In 12 eyes (36%), visual acuity improved 0.1 logMAR or more, in 12 eyes (36%), vision was unchanged (gain or loss of 0-0.05 logMAR), and in nine eyes (27%), vision decreased 0.1 logMAR or more. Mean central foveal thickness (CFT) on optical coherence tomography (OCT) scan was 412 µm (95% CI 390-434 µm) before injections. After injections, the mean CFT decreased to 352 µm (95% CI 334-370 µm). The mean reduction in CFT was 14% (95% CI 4-24%, p = 0.01). Sixteen eyes (48.5%) became devoid of oedema on the last OCT scan. Despite the significant reduction in CFT, the visual acuity remained unchanged. CONCLUSION: Intravitreal ranibizumab can be effective in previously vitrectomized eyes with diabetic macular oedema. However, the response is variable and should be carefully monitored.

The IGF-Axis and Diabetic Retinopathy Before and After Gastric Bypass Surgery.

BACKGROUND: Laparoscopic gastric bypass (LGB) abruptly causes remission of type 2 diabetes (T2D). Such dramatic metabolic changes have previously been found to cause worsening of diabetic retinopathy (DR) and circulating insulin-like growth factor I (IGF-I) has been suggested as a causal mediator. We aimed to evaluate baseline imbalances in the circulating IGF-system and changes after LGB in patients with T2D. METHODS: Prospective ocular examinations and measurement of the IGF-axis before and 3 and 12 months after LGB. IGF-bioactivity was measured by cell-based IGF-I receptor (IGF-IR) kinase activation assay (bioactive IGF). Total IGF-I, IGF-II and IGF binding protein (IGFBP) 1 and 3 were determined by immunoassays. RESULTS: At baseline, 18 of 36 patients presented with DR. These patients had higher levels of bioactive IGF (p = 0.03) than patients without DR and this association was strengthened in multivariate analysis (p = 0.006). Three patients had worsening of DR, unrelated to other markers. In univariate analysis, bioactive IGF increased at 3 months (p = 0.05) but this change became insignificant in multivariate analysis (p = 0.11). IGFBP-1 increased whereas IGFBP-3 and total IGF-II decreased at the two postoperative visits (p ≤ 0.001). Total IGF-I showed no significant changes. HbA1c, glucose, HOMA-IR and lipids improved after surgery. Two patients did not complete the 12-month visit. CONCLUSIONS: In obese T2D patients, bioactive IGF is a potential biomarker for DR and levels tended to increase 3 months after bariatric surgery. IGFBP-1 increased while IGFBP-3 and total IGF-II decreased postoperatively, but these changes were unassociated with the development of DR. Markers of the metabolic syndrome improved.

Thickening of inner retinal layers in the parafovea after bariatric surgery in patients with type 2 diabetes.

PURPOSE: Bariatric surgery dramatically improves the metabolic profile in patients with type 2 diabetes (T2D). We have previously reported a thickening of the retina after bariatric surgery and aimed to investigate these subclinical changes in retinal thickness and vessel calibres in more detail. METHODS: We examined 51 patients with T2D 2 weeks before and 1, 3, 6 and 12 months after bariatric surgery. Retinal thickness was measured with optical coherence tomography and automated segmentation in the fovea, parafovea and perifovea in each retinal layer. Retinal vessels were semiautomatically measured in a zone 0.5-1 disc diameters from the optic disc. RESULTS: The total macula thickened with a peak after 6 months in both univariate (2.7 ± 0.4 µm, p < 0.001) and multivariate analysis (2.2 ± 0.7 µm, p = 0.001). The thickening was most prominent in the parafoveal ring 1-3 mm from the centre and in the retinal nerve fibre layer and outer nuclear layer. A fall in HbA1c (p = 0.01) and longer duration of diabetes (p = 0.01) were associated with more thickening. The central retinal artery equivalent widened 22.1 µm (±8.9, p = 0.01) in the multivariate analysis 12 months postoperatively. A reduction in blood pressure was associated with less widening of the arterioles (p = 0.01). CONCLUSION: Patients with T2D had thickening of the retina after gastric bypass surgery with a peak 6 months postoperatively. The thickening was most pronounced in the retinal nerve fibre layer and the outer nuclear layer of the parafovea. In multivariate analysis, the central retinal artery equivalent increased at 12 months.

Monitoring of Diabetic Retinopathy in relation to Bariatric Surgery: a Prospective Observational Study.

BACKGROUND: To investigate the need for closer perioperative monitoring of diabetic retinopathy in patients with type 2 diabetes undergoing bariatric surgery. METHODS: Prospective observational clinical study of 56 patients with type 2 diabetes undergoing bariatric surgery. The patients were examined with 7-field fundus images and optical coherence tomography scans 2 weeks before and 1, 3, 6 and 12 months after bariatric surgery. Worsening was defined as a two-step change in the Wisconsin Epidemiologic Study of Diabetic Retinopathy scale or appearance or worsening of macular edema. Postoperative changes were analyzed in a mixed model. RESULTS: Six patients (11 %) had any worsening at any visit, and three (5 %) persisted at 1 year. Of the 24 patients with preoperative retinopathy, 4-13 % worsened and 9-22 % improved, with significant overall improvement at 6 months (p = 0.01). Only one (3%) of the 32 patients without preoperative diabetic retinopathy had a transient worsening at 6 months. No patients developed macular edema, but the whole cohort had a minor increase in center point foveal thickness that peaked 6 months postoperatively. The patients were required to have good glucose control preoperatively where HbA1c was 6.4 ± 1.9 %. CONCLUSIONS: Diabetic retinopathy was clinically stable after bariatric surgery, and none of the observed changes would have resulted in a changed screening interval at our center. This supports adherence to regular diabetic retinopathy screening guidelines following bariatric surgery in well-controlled patients. A clinically negligible but statistically significant foveal thickening 6 months postoperatively warrants further study.

[Standard ballpoint pens disappear from the coats with a half-life of nine days].

UNLABELLED: Ballpoint pens are important tools for the daily work of the physicians. However, a practical challenge seems to be that they disappear just when one needs them most. We call this the ballpoint pen paradox. We have studied the fate of 60 ballpoint pens in an outpatient clinical setting. Five physicians, five nurses and five medical secretaries were equipped with four barcode-tagged ballpoint pens. During follow-ups, we systematically searched the participants' coat and the department for the barcode-tagged ballpoint pens. We illustrated the migration of the ballpoint pens using a diagram and tested fit of linear and exponential trend line. The ballpoint pens displayed a tremendous migration in the department. Disappearance from the coat was exponentially with a half-life of 9 days - only 23% were left after 18 days. Disappearance from the department was linear with a 3% loss per day - only 42% were left after 18 days. Ballpoint pens have a high migration and turnover rate. The fate is unknown for a great amount of ballpoint pens. They are treated carelessly, which finally results in waste of time and resources. It may be that the ballpoint pen paradox can be diminished by phasing out ballpoint pens of low quality. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

Intravitreal ranibizumab for retinal vein occlusion through 1 year in clinical practice.

PURPOSE: To evaluate the efficacy and safety of intravitreal ranibizumab for branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO) in daily clinical practice. METHODS: A prospective study enrolling all patients diagnosed with BRVO or CRVO who received intravitreal ranibizumab therapy at our department. RESULTS: Fifty-seven patients had BRVO and 49 had CRVO. By 12 months, the patients with BRVO improved a mean of 11.6 (P < 0.0001) ETDRS (Early Treatment Diabetic Retinopathy Study) letters, whereas the patients with CRVO improved a mean of 1.8 letters (P = 0.50). The proportion of patients gaining ≥ 15 ETDRS letters was 26.3% for BRVO and 16.7% for CRVO. The proportion of patients losing ≥ 15 ETDRS letters was 0% for BRVO and 8.3% for CRVO. The reduction in foveal center point thickness at 12 months was 248 µm for BRVO (P < 0.0001) and 222 µm for CRVO (P < 0.0001). Functional outcome did not mirror anatomical outcome, and younger patients had better outcome. CONCLUSION: Our 12-month results of BRVO treated with intravitreal ranibizumab in daily clinical practice are similar to the results of the BRAVO trial that led to the approval of the therapy. However, our results for CRVO failed to reproduce the results of the CRUISE trial.

No cases of endophthalmitis after 20,293 intravitreal injections in an operating room setting.

BACKGROUND: Intravitreal injection has become a common procedure worldwide. A rare, but sight threatening, complication is bacterial endophthalmitis that has a poor visual prognosis. To identify practices that minimize the risk of endophthalmitis, the setting of a Danish University hospital is described. METHODS: A review of the intravitreal injection database of the department. All injections were performed in a positive pressure ventilated operating room under sterile conditions. The treating physicians wore face mask, the conjunctiva was irrigated twice with 5% povidone-iodine preoperatively, and topical tobramycin was applied immediately after the injection. RESULTS: The authors have performed a total of 20,293 injections were performed in 2,575 eyes. No cases of proven or suspected endophthalmitis were identified corresponding to a risk of 0% (95% confidence interval, 0-0.019) per injection and 0% (95% confidence interval, 0-0.15%) per patient. Approximately 7,000 injections, all in patients without diabetes, were treated without a course of topical antibiotics after the injection. CONCLUSION: The department has had the lowest rate of endophthalmitis after intravitreal injections in the current literature. Several factors that could have contributed to the positive result are highlighted. Omitting a postoperative course of topical antibiotic appears safe in patients without diabetes.

Longstanding refractory pseudophakic cystoid macular edema resolved using intravitreal 0.7 mg dexamethasone implants.

BACKGROUND: Refractory pseudophakic cystoid macular edema (PCME) following cataract surgery has long posed a challenge to clinicians, but intravitreal injections with a sustained delivery 0.7 mg dexamethasone implant has emerged as a promising therapy for this condition. OBJECTIVE: To present a case of longstanding and refractory PCME with complete remission through 189 days of follow-up after two successive injections with intravitreal dexamethasone implants. CASE REPORT: A 59-year-old male had experienced metamorphopsia for approximately 4 years and had been diagnosed with PCME 15 months earlier. Since the time of the diagnosis, the condition had been refractory to both subtenon triamcinolone acetonide and a total of five injections with intravitreal ranibizumab. After the last injection with ranibizumab, central subfield mean thickness was 640 µm, and the best corrected visual acuity was 78 Early Treatment Diabetic Retinopathy Study letters. Following an intravitreal injection with a dexamethasone implant, the macular edema resolved at the next follow-up. The macular edema returned 187 days after the first injection and was treated with another intravitreal dexamethasone implant. Again, the macular edema subsided completely, and best corrected visual acuity improved to 84 Early Treatment Diabetic Retinopathy Study letters, a condition which was maintained through an additional 189 days of follow-up. CONCLUSION: Chronic PCME is traditionally a difficult condition to treat, but we are encouraged by the optimal response experienced with intravitreal sustained release dexamethasone implants in our patient whose longstanding PCME had been refractory to previous treatments with both subtenon triamcinolone and intravitreal ranibizumab. In this case, the condition appeared to be fully reversible once inflammation was controlled, but the need for monitoring and repeated injections remains an issue of concern.