Associations between Serial Intravitreal Injections and Dry Eye.

PURPOSE: To investigate the effects of serial intravitreal injections (IVIs) on the ocular surface and meibomian glands (MGs) in patients treated with anti-vascular endothelial growth factor (anti-VEGF) for neovascular age-related macular degeneration (nAMD). DESIGN: Retrospective, controlled, observational study. PARTICIPANTS: Patients with nAMD receiving unilateral IVIs with anti-VEGF agents. The fellow eye was used as control. METHODS: Tear film and ocular surface examinations were performed on a single occasion at a minimum of 4 weeks after IVI. A pre-IVI asepsis protocol with povidone-iodine (PVP-I) was applied. MAIN OUTCOME MEASURES: Upper and lower MG loss, tear meniscus height (TMH), bulbar redness (BR) score, noninvasive tear break-up time (NIBUT), tear film osmolarity (TOsm), Schirmer test, corneal staining, fluorescein tear film break-up time (TBUT), meibomian gland expressibility (ME), and meibum quality. RESULTS: Ninety patients with a mean age of 77.5 years (standard deviation [SD], 8.4; range 54-95) were included. The median number of IVIs in treated eyes was 19.5 (range, 2-132). Mean MG loss in the upper eyelid was 19.1% (SD, 11.3) in treated eyes and 25.5% (SD, 14.6) in untreated fellow eyes (P = 0.001). For the lower eyelid, median MG loss was 17.4% (interquartile range [IQR], 9.4-29.9) in treated eyes and 24.5% (IQR, 14.2-35.2) in fellow eyes (P < 0.001). Mean BR was 1.32 (SD, 0.46) in treated eyes versus 1.44 (SD, 0.45) in fellow eyes (P = 0.017). Median TMH was 0.36 mm (IQR, 0.28-0.52) in treated eyes and 0.32 mm (IQR, 0.24-0.49) in fellow eyes (P = 0.02). There were no differences between treated and fellow eyes regarding NIBUT, TOsm, Schirmer test, corneal staining, fluorescein TBUT, ME, or meibum quality. CONCLUSIONS: Repeated IVIs with anti-VEGF with preoperative PVP-I application was associated with reduced MG loss, increased tear volume, and reduced signs of inflammation compared with fellow nontreated eyes in patients with nAMD. This regimen may thus have a beneficial effect on the ocular surface. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

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.

EN FACE IMAGING OF OUTER RETINAL PATHOLOGY AFTER RETINAL DETACHMENT.

PURPOSE: To explore the potentials of multicolor (MC) confocal scanning laser ophthalmoscopy (cSLO) to detect structural retinal pathology after macula-off rhegmatogenous retinal detachment (RRD) and to describe their appearances. METHODS: Thirty MC cSLO images of 30 eyes after RRD repair were prospectively studied for the presence of RRD-related pathology. All MC cSLO findings were verified using swept source optical coherence tomography. Positive percent agreements were calculated using swept source optical coherence tomography as reference. RESULTS: Eight RRD-related structural pathologies were identified and characterized: ellipsoid zone (EZ) disruption, foveal EZ rosette, outer retinal fold, retinal detachment line, subretinal fluid blebs, subretinal fluid layer, retinal striae, and intraretinal cysts. Multicolor cSLO positive percent agreements were as follows: EZ disruption: 79%, foveal EZ rosette: 73%, outer retinal fold: 67%, retinal detachment line: 84%, subretinal fluid blebs: 0.70%, subretinal fluid layer: 50%, intraretinal cysts: 60%, and retinal striae: 100%. CONCLUSION: En face MC cSLO imaging detected and delineated RRD-related structural pathology in high agreement with cross-sectional swept source optical coherence tomography and can supplement optical coherence tomography in the documentation and monitoring of outer retinal remodeling processes after macula-off RRD. Foveal EZ rosette is a new finding of the foveal EZ.

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.

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.

AIR TAMPONADE COMBINED WITH NONSUPINE POSITIONING IN MACULAR HOLE SURGERY FOR PSEUDOPHAKIC EYES.

PURPOSE: To investigate the closure rate of primary full-thickness macular hole, following intraocular air tamponade combined with a nonsupine positioning regimen. METHODS: A prospective study of patients with full-thickness macular hole, who underwent pars plana vitrectomy with internal limiting membrane peeling and intraocular air tamponade followed by 3 days of nonsupine positioning. Outcome measures were primary full-thickness macular hole closure and improvement in best-corrected visual acuity after 6 months. RESULTS: A total of 34 eyes were included. In the group of full-thickness macular hole ≤400 µm, primary closure occurred in 95% (19/20), whereas only 57% (8/14) of those >400 µm closed (P = 0.01). The mean gain in best-corrected visual acuity was 3.5 ETDRS (Early Treatment Diabetic Retinopathy Study) lines (SD = 1.5) (P < 0.01). The air bubble meniscus height at the first postoperative day was estimated to a mean of 59% (range, 50-70%), at the second postoperative day it was 46% (range, 40-55%), and the third day it was 39% (range, 30-45%). Mean intraocular air bubble duration was 10 days (range, 8-13 days). CONCLUSION: The combination of air tamponade and nonsupine positioning regimen leads to high closure rates for small/medium macular holes (≤400 µm), but not for large macular holes (>400 µm).

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.

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.

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.