Air versus Sulfur Hexafluoride Gas Tamponade for Small and Medium-Sized Macular Holes: A Randomized Noninferiority Trial.

PURPOSE: To investigate whether air tamponade is noninferior to sulfur hexafluoride (SF6) gas tamponade for small (≤ 250 µm) and medium-sized (> 250 µm and ≤ 400 µm) macular holes (MHs). DESIGN: Multicenter, randomized controlled, noninferiority trial. PARTICIPANTS: Patients aged ≥ 18 years undergoing surgery for primary MHs of ≤ 400 µm in diameter. METHODS: The patients in both groups underwent conventional pars plana vitrectomy with peeling of the internal limiting membrane. At the end of the surgery, the patients were randomized to receive either air or SF6 gas tamponades, stratified by MH size. Postoperatively, the patients followed a nonsupine positioning regimen for 3 days. MAIN OUTCOME MEASURES: The primary end point was the MH closure rate after a single surgery, confirmed by OCT after 2 to 8 weeks. The noninferiority margin was set at a 10-percentage-point difference in the closure rate. RESULTS: In total, 150 patients were included (75 in each group). In the intention-to-treat (ITT) analysis, 65 of 75 patients in the air group achieved primary closure. All 75 MHs in the SF6 group closed after a single surgery. Six patients were excluded from the per-protocol (PP) analysis. In the PP analysis, 63 of 70 patients in the air group and all 74 patients in the SF6 group achieved MH closure after a single surgery, resulting in closure rates of 90% (95% confidence interval [CI], 79.9%-95.5%) and 100% (95% CI, 93.9%-100%), respectively. For the difference in closure rates, the lower bound of a 2-sided 95% CI exceeded the noninferiority margin of 10% in both ITT and PP analyses. In the subgroups of small MHs, all 20 patients in the air group and all 28 patients in the SF6 group achieved primary closure. CONCLUSIONS: This prospective randomized controlled trial proved that air tamponade is inferior to SF6 tamponade for MHs of ≤ 400 µm in diameter.

Clinical course, treatment and visual outcome of an outbreak of Burkholderia contaminans endophthalmitis following cataract surgery.

BACKGROUND: Postoperative endophthalmitis is a rare but dreaded complication of intraocular surgery and often results in severe visual impairment or blindness. The present study describes the clinical course, treatment and visual outcome of an outbreak of Burkholderia contaminans endophthalmitis following cataract surgery. METHODS: Among 290 patients who underwent uneventful phacoemulsification cataract surgery at one outpatient clinic between January 4th and 28th 2019, 6 cases developed Burkholderia contaminans endophthalmitis. Clinical data were collected by retrospective review of patient records. Microbiological samples from vitreous aspirates, intraocular lenses (IOL) and lens capsules were cultured, and recA and draft whole genome sequences analysed. RESULTS: The recA sequences of all Burkholderia contaminans isolates and the allelic profile of the isolates were identical. All cases had a similar clinical presentation with rapid development of endophthalmitis symptoms with variable time to onset. The mean time to admission was 34 days (12-112 days). All cases had a seemingly favourable response to intravitreal antibiotics. However, acute recurrences occurred after long time periods (12-71 days). The cases experienced between 0 and 3 recurrences. Due to persistent infection, the cases received between 5 and 15 treatments (mean 7.8) including IOL and lens capsule explantation in 5 of 6 cases. Burkholderia contaminans was detected in all explanted lens capsules. The final corrected distance visual acuity (CDVA, Snellen chart) was between 0.8 and 1.2 and all cases had final CDVA ≥0.8. CONCLUSIONS: A persistent and intensive treatment approach including total lens capsule and IOL explantation is recommended for Burkholderia contaminans endophthalmitis following cataract surgery and may lead to a favourable visual result.

STRUCTURAL PATHOLOGY AFTER RETINAL DETACHMENT: Multicolor Confocal Scanning Laser Ophthalmoscopy Versus Color Fundus Photography.

PURPOSE: To compare pathology detection using multicolor confocal scanning laser ophthalmoscopy with color fundus photography following macula-off rhegmatogenous retinal detachment. METHODS: Postsurgery multicolor confocal scanning laser ophthalmoscopy and color fundus photography images from 30 rhegmatogenous retinal detachment patients were examined by 10 masked graders. Imaging was performed with the Heidelberg Spectralis HRA and the digital retinal camera Basler acA2500-14gc GigE. Swept-source optical coherence tomography was used as verification modality. Detection rates of ellipsoid zone disruption, foveal ellipsoid zone rosette, outer retinal folds, intraretinal cysts, subretinal fluid layer, subretinal fluid blebs, retinal striae, and retinal detachment line were compared. Intermodality and intergrader agreement were estimated. RESULTS: Overall pathology detection was significantly higher for multicolor confocal scanning laser ophthalmoscopy multicolor confocal scanning laser ophthalmoscopy (adjusted odds ratio = 7.39; 95% confidence interval, 1.64-33.30; P = 0.009). The intermodality and intergrader agreement on overall pathology detection were moderate. The intermodality agreement was 0.49 (95% confidence interval, 0.48-0.51; P < 0.0001) (Gwet's AC1). Intergrader agreement was 0.53 (95% confidence interval, 0.52-0.54; P < 0.0001) for multicolor confocal scanning laser ophthalmoscopy and 0.58 (95% confidence interval, 0.57-0.59; P < 0.0001) (Fleiss kappa) for color fundus photography. CONCLUSION: Multicolor confocal scanning laser ophthalmoscopy imaging is superior to color fundus photography in detecting and delineating structural retinal abnormalities following rhegmatogenous retinal detachment and can be a helpful tool in the visualization of retinal remodeling processes in patients recovering from rhegmatogenous retinal detachment surgery.

Nonsupine Positioning after Macular Hole Surgery: A Prospective Multicenter Study.

PURPOSE: To evaluate the postoperative closure rate of full-thickness macular holes (MHs) after nonsupine positioning, which means that the patients avoid upward gaze and a supine sleeping position, and to investigate the correlation between postoperative positioning compliance and closure rate. DESIGN: Prospective, multicenter study (ClinicalTrials.gov identifier, NCT02295943). PARTICIPANTS: Patients undergoing primary surgery for primary MH. METHODS: Patients underwent pars plana vitrectomy with internal limiting membrane peeling and sulfur hexafluoride gas tamponade followed by 3 to 5 days of nonsupine positioning. A positioning measuring device that recorded the time spent in the supine position was attached to patients' forehead after surgery for 24 hours. MAIN OUTCOME MEASURES: Anatomic closure rate of MH at 2 weeks or more after surgery and the time spent in supine position during the first 24 hours after surgery. RESULTS: A total of 205 participants were included, of whom 2 were lost to follow-up. Two hundred two of 203 MHs closed after a single operation, giving a closure rate of 99.5% (95% confidence interval, 97.3%-99.9%). The median time of supine positioning during the first 24 hours was 28 seconds (range, 0:00:00-01:52:28). Because of the very high closure rate, a correlation between positioning compliance and closure rate could not be established. CONCLUSIONS: Pars plana vitrectomy with internal limiting membrane peeling followed by a short-term nonsupine positioning accomplished a very high MH closure rate. Thus, face-down positioning was not necessary to achieve excellent closure rates in this study.

Ranibizumab or Bevacizumab for Neovascular Age-Related Macular Degeneration According to the Lucentis Compared to Avastin Study Treat-and-Extend Protocol: Two-Year Results.

PURPOSE: To compare the efficacy and safety of bevacizumab (Avastin; F. Hoffmann-La Roche Ltd, Basel, Switzerland) versus ranibizumab (Lucentis; Novartis Pharma AG, Basel, Switzerland) for neovascular age-related macular degeneration (nAMD) after 2 years when using a treat-and-extend protocol. DESIGN: Multicenter, randomized, noninferiority trial with a noninferiority limit of 5 letters. PARTICIPANTS: Patients 50 years of age or older with previously untreated nAMD in 1 eye and best-corrected visual acuity 20/25 to 20/320. METHODS: Patients were assigned randomly to receive intravitreal injections with either ranibizumab 0.5 mg or bevacizumab 1.25 mg. Injections were given every 4 weeks until inactive disease was achieved. The treatment interval then was extended by 2 weeks at a time up to a maximum of 12 weeks. In the event of a recurrence, the treatment interval was shortened by 2 weeks at a time. MAIN OUTCOME MEASURE: Mean change in visual acuity at 2 years. RESULTS: Of a total of 441 randomized patients, 339 patients (79%) completed the 2-year visit. According to per-protocol analysis at 2 years, bevacizumab was equivalent to ranibizumab, with 7.4 and 6.6 letters gained, respectively (95% confidence interval [CI] of mean difference, -4.1 to 2.5; P = 0.634). Intention-to-treat analysis was concordant, with a gain of 7.8 letters for bevacizumab and 7.5 letters for ranibizumab (95% CI of mean difference, -3.2 to 2.7; P = 0.873). The 2-year results did not show any significant difference in mean central retinal thickness, with a decrease of -113 µm for bevacizumab and -122 µm for ranibizumab (95% CI of mean difference, -32 to 15; P = 0.476). There was a statistically significant difference between the drugs regarding the number of treatments given, with 18.2 injections for bevacizumab and 16.0 injections for ranibizumab (95% CI of mean difference, -3.4 to -1.0; P ≤ 0.001). The number of serious adverse events was similar between the groups over the course of the study. CONCLUSIONS: At 2 years, bevacizumab and ranibizumab had an equivalent effect on visual acuity and reduction of central retinal thickness when administered according to a treat-and-extend protocol for nAMD. There was no significant difference in the number of serious adverse events between the treatment groups.

Efficacy of ranibizumab in patients with macular edema secondary to central retinal vein occlusion: results from the sham-controlled ROCC study.

PURPOSE: The ROCC study (randomized study comparing ranibizumab to sham in patients with macular edema secondary to central Retinal vein OCClusion [CRVO]) evaluated the short-term effect of intravitreal ranibizumab injections on best-corrected visual acuity (BCVA) and macular edema. DESIGN: Prospective, multicenter, randomized, double-masked, placebo-controlled trial. METHODS: In this 6-month trial, 32 patients with macular edema secondary to CRVO were randomized to receive monthly intravitreal ranibizumab (0.5 mg/0.05 mL) or sham injections for 3 consecutive months. If macular edema persisted, patients received further monthly injections. Primary outcome measures were BCVA and central macular thickness (CMT) at 6 months. RESULTS: Twenty-nine patients completed the study. After 3 months, BCVA improved by a mean +/- standard deviation (SD) of 16 +/- 14 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in the ranibizumab group (n = 15), compared with a mean loss of 5 +/- 15 ETDRS letters in the sham group (n = 14; P = .001). The mean +/- SD change in CMT was -411 +/- 200 microm in the ranibizumab group and -86 +/- 165 microm with sham (P < .001). At 6 months, the mean +/- SD change in BCVA was 12 +/- 20 ETDRS letters in the ranibizumab group compared with -1 +/- 17 ETDRS letters in the sham group (P = .067). The mean +/- SD change in CMT was -304 +/- 194 microm with ranibizumab and -151 +/- 205 microm with sham (P = .05). Twelve patients (80%) in the ranibizumab group required more than 3 initial injections; mean +/- SD number of injections was 4.3 +/- 0.9 during the study. CONCLUSION: Monthly ranibizumab significantly increased BCVA and decreased macular edema, compared with sham, in patients with CRVO. Repeated consecutive injections are necessary to maintain initial positive results.

Retinal artery occlusion following intravitreal anti-VEGF therapy.

PURPOSE: Anti-vascular endothelial growth factor (anti-VEGF) therapy effectively inhibits angiogenesis and is now enjoying widespread use in the treatment of age-related macular degeneration (AMD). It may also have a role in the treatment of macular oedema secondary to other conditions. VEGF is a signalling molecule that has a variety of roles, including vasoregulation and effects on the coagulation homeostasis. Anti-VEGF therapy may therefore have adverse effects on ocular blood flow. METHODS: Two cases of retinal artery occlusion after intravitreal injection of anti-VEGF are presented. Both patients were given the treatment to reduce macular oedema secondary to central retinal vein occlusion. Possible mechanisms are discussed. RESULTS: Patient 1 developed a central retinal artery occlusion within 1 month of an intravitreal injection of ranibizumab (Lucentis). The macular oedema was totally resolved at 1 month; final visual acuity (VA) was light perception. Patient 2 developed a branch retinal artery occlusion in the macula 2 days after an intravitreal injection of bevacizumab (Avastin). The macular oedema was almost resolved within 1 week and did not recur; final VA was 0.6. CONCLUSIONS: Anti-VEGF therapy may have a role in the treatment of macular oedema caused by central retinal vein occlusions. However, our report indicates that the therapeutic principle may be associated with an increased risk of retinal arterial occlusions.

The potential of digital monochrome images versus colour slides in telescreening for diabetic retinopathy.

We explored the potential of digital monochrome images as an alternative to colour slides in screening for diabetic retinopathy. Twenty-eight patients with diabetes were recruited for the study and 20 actually participated. Using a fundus camera (Nikon 505AF) one set of three digital images and one set of three colour slides were taken per eye. Two independent ophthalmologists graded the colour slides and the digital images for diabetic retinopathy. The ophthalmologists spent about two minutes grading each set of images, suggesting that specialists could potentially screen a large number of patients. The agreement between the two screening methods was 0.95 and 0.89, with respect to disease or no disease. The agreement (kappa) between the two ophthalmologists for grade of retinopathy was 0.47 when colour slides were employed and 0.61 when digital monochrome images were employed. The results indicate that digital red-free monochrome images represent a superior screening tool for diabetic retinopathy. Tele-screening may be beneficial when patients have to travel substantial distances to visit an ophthalmologist.

An economic analysis of screening for diabetic retinopathy.

The costs of telemedicine screening for diabetic retinopathy were examined in a trial conducted in northern Norway, involving the University Hospital of Tromsø (UHT) and the primary care centre in Alta, approximately 400 km away. In Alta, specially trained nurses examined 42 diabetic patients using a digital camera to obtain images of the retina. The images were then sent by email to an eye specialist at the UHT. A cost-minimization analysis showed that at low workloads, for example 20 patients per annum, telemedicine was more expensive than conventional examination: NKr8555 versus NKr428 per patient. However, at higher workloads, telemedicine was cheaper. For example, at 200 patients per annum, telemedicine cost NKr971 and conventional examination cost NKr1440 per patient. The break-even point occurred at a patient workload of 110 per annum. Given that there are some 250 diabetic patients in Alta, telemedicine screening is the cheaper service for the public sector.