Tear cytokine levels are reduced in patients treated with intravitreal injections.

PURPOSE: To investigate cytokine levels in the tear fluid of patients receiving serial intravitreal injections (IVI) with anti-vascular endothelial growth factor (anti-VEGF) for neovascular age-related macular degeneration (nAMD). METHODS: Concentrations of six cytokines (IFN-γ, IL-1ß, IL-6, IL-8, TNF and VEGF) in tears of patients receiving anti-VEGF in one eye were assayed using multiplex cytometric bead array. The fellow untreated eye served as control. Tear sampling was performed on a single occasion at a minimum of four weeks after IVI. Patients underwent a pre-IVI antisepsis protocol with povidone-iodine. RESULTS: Tear fluid from thirty patients with a mean age of 78.8 years (range 58-90) was assayed. Subjects received a median of 43.5 (range 22-106) IVI in one eye. The median level of IFN-γ was 0.33 (interquartile range (IQR) 0.22-0.52) pg/mg of total protein in injected eyes versus 0.41 (IQR 0.21-1.05) pg/mg in fellow eyes (p = 0.017). For TNF, a median level of 0.12 (IQR 0.08-0.18) pg/mg of total protein was found in injected eyes versus 0.14 (IQR 0.07-0.33) pg/mg of total protein in fellow eyes (p = 0.019). There were no differences between injected and fellow eyes regarding the levels of IL-1ß, IL-6, IL-8 and VEGF. CONCLUSION: Tear fluid in eyes receiving serial IVI with anti-VEGF and preoperative povidone-iodine antisepsis constitutes lower levels of the pro-inflammatory cytokines IFN-γ and TNF compared to fellow eyes. This provides biochemical support of previous findings of reduced signs of inflammation and healthier tear film parameters in patients treated with serial IVI.

LONG-TERM CHANGES IN VISUAL FUNCTION AND EN FACE OPTICAL COHERENCE TOMOGRAPHY FINDINGS IN FOVEA-OFF RETINAL DETACHMENT: A 2-Year Prospective Study.

PURPOSE: To investigate the long-term changes in visual function and outer retinal abnormalities on en face optical coherence tomography after fovea-off rhegmatogenous retinal detachment and to assess associations between functional outcomes and outer retinal abnormalities. METHODS: Prospective, observational study. The following data were collected at 1, 3, 6, 12, and 24 months after retinal reattachment: Best-corrected visual acuity, metamorphopsia (M-CHARTS), aniseikonia (New Aniseikonia Test), altered ellipsoid zone reflectivity, outer retinal folds, macular detachment demarcation, and subfoveal fluid. RESULTS: Thirty-eight patients were included. Best-corrected visual acuity improved significantly from 1 to 12 months and from 12 to 24 months (P < 0.001; P = 0.022). Vertical and horizontal metamorphopsia improved significantly from 1 to 12 months (P < 0.001; P = 0.002), and at 24 months, scores of ≥0.2° were present in 54% and 42% of patients, respectively. The degree of aniseikonia did not change. Best-corrected visual acuity and aniseikonia scores were positively associated with outer retinal fold (r 0.4, P = 0.009; r 0.4, P = 0.048). A gradual normalization of outer retinal reflectivity took place during 24 months. CONCLUSION: Visual acuity improved significantly during the second year after reattachment surgery for fovea-off rhegmatogenous retinal detachment, in parallel with normalization of outer retinal abnormalities on en face optical coherence tomography. Metamorphopsia did not improve after 12 months, and aniseikonia remained unchanged.

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.

Optical coherence tomography features and risk of macular hole formation in the fellow eye.

BACKGROUND: To investigate the risk of primary macular hole (MH) in the fellow eye, and to evaluate baseline characteristics and optical coherence tomography (OCT) features that precede MH formation in the fellow eye. METHODS: A retrospective review of 229 patients treated for primary MH at Stavanger University Hospital, Norway, from January 2008 through December 2018. The patients were categorised into two groups according to subsequent development of MH in the fellow eye. The OCT findings of the two groups were compared, and associated risk factors for MH formation assessed. RESULTS: Twenty cases of bilateral MH were identified. The overall bilateral disease risk was 8.8% (95% CI, 5.8-13.2%). Two patients were previously operated in the fellow eye, six patients presented with bilateral MH, and 12 patients subsequently developed MH in the fellow eye. The risk of subsequent MH development was 5.7% (95% CI, 3.3-9.8%). Although the extent of posterior vitreous detachment (PVD) tended to be more progressed in the bilateral group compared with the unilateral group, the difference was not statistically significant. In the bilateral group, 41.7% had outer retinal defects vs 6.6% in the unilateral group (p = 0.001), and 33.3% in the bilateral group had intraretinal pseudocysts vs 10.2% in the unilateral group (p = 0.036, not significant after multiple testing correction). CONCLUSION: Outer retinal defects and intraretinal pseudocysts are associated with an increased risk of MH formation in the fellow eye, and complete PVD indicates a decreased risk of MH formation.

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.

Epidemiology and morphology of full-thickness macular holes.

PURPOSE: To investigate the incidence of full-thickness macular holes (FTMHs) and their morphological features according to the International Vitreomacular Traction Study (IVTS) classification. METHODS: The clinical records of all new patients with FTMH, referred between 2008 and 2014, were reviewed for demographics, cause of the FTMH, age at diagnosis, symptom duration, laterality, visual acuity (VA), axial length and lens status. A detailed analysis of the patients' spectral domain optical coherence tomography (SD-OCT) images was performed, and the primary FTMHs were classified in clinical stages according to the IVTS classification. From the SD-OCT, accurate macula drawings were made by means of a computer-drawing software. By merging these drawings and displaying them as colour-coded maps, the morphology and shape of the FTMH were visualized. RESULTS: The study included 177 eyes (152 primary and 25 secondary FTMH) in 166 patients. In primary FTMH, the male-to-female ratio was 1:2.2. The age- and gender-adjusted annual incidences of primary FTMH were 7.9 eyes and 7.4 individuals per 100 000 inhabitants. Mean primary FTMH minimum linear diameter (MLD) and basal diameter (BD) were 435 µm and 872 µm, respectively, and 13% were classified as small, 31% as medium and 55% as large. Vitreomacular traction (VMT) and epiretinal membrane (ERM) were present in 34% and 36% of the eyes, respectively. CONCLUSION: This study provides data on the incidence rates of FTMH adjusted to different standard populations. The morphological analysis and novel computational visualization technique offer new insight into the structural complexity of FTMH and how VMT and ERM significantly influence FTMH configuration.