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.

Reticular Pseudodrusen Voids after Rhegmatogenous Retinal Detachment.

We present a case of reticular pseudodrusen (RPD) regression on multimodal retinal imaging following a rhegmatogenous retinal detachment. Two mechanisms of action can be postulated. The subretinal deposits dissolve due to voluminous subretinal fluid during retinal separation from the retinal pigment epithelium and are in turn mechanically cleared during retinal re-attachment surgery. Alternatively, an RPD clearance is facilitated by enhanced phagocytic activity of macrophages and microglial cells as a response to acute retinal stress.

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.

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.

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.

Exposure to antazoline-naphazoline eye drops during pregnancy and the risk of congenital malformations: a Danish nationwide cohort study.

PURPOSE: To investigate whether exposure to antazoline-naphazoline eye drops in the first trimester of pregnancy was associated with an increased risk of malformations in humans. METHODS: All women giving live birth between 1997 and 2011 in Denmark were included in this nationwide cohort study. All women redeeming at least one prescription of antazoline-naphazoline eye drops during the first 84 days of pregnancy were identified. Logistic regression was used to estimate the odds ratios of malformations among exposed offspring compared to non-exposed offspring. RESULTS: We identified 977 706 births between 1997 and 2011. A total of 3061 women (0.32%) were exposed to antazoline-naphazoline eye drops in the first trimester of pregnancy. The rate of congenital malformations was 3.0% (n = 93) in exposed offspring and 3.5% (n = 33 594) in unexposed offspring. First-trimester exposure to antazoline-naphazoline was not associated with major congenital malformations overall (odds ratio: 0.88, 95% confidence interval: 0.71-1.09) or with any specific major malformation. The number of redeemed prescriptions was unchanged during all trimesters of pregnancy as compared to before and after pregnancy (p < 0.05). CONCLUSION: Exposure to antazoline-naphazoline eye drops in the first trimester of pregnancy appears not to be associated with increased teratogenic risk.

Exposure to topical chloramphenicol during pregnancy and the risk of congenital malformations: a Danish nationwide cohort study.

PURPOSE: To investigate whether exposure to topical chloramphenicol in the first trimester of pregnancy is associated with congenital malformations. METHODS: The authors conducted a nationwide cohort study including all women giving live birth between 1997 and 2011 in Denmark. All women redeeming at least one prescription of chloramphenicol eye drops or eye ointment during the first 84 days of pregnancy were identified. Logistic regression was used to estimate the odds ratios of malformations among exposed women compared to non-exposed women. RESULTS: 966 372 births between 1997 and 2011 were included. A total of 6024 women were exposed to topical chloramphenicol in the first trimester. The rate of congenital malformations was 3.50% among offspring of exposed mothers and 3.49% among unexposed. Exposure to topical chloramphenicol in the first trimester was not associated with major congenital malformations (adjusted odds ratio = 1.06, 95% CI 0.91-1.22) or specific major malformations. The number of redeemed prescriptions decreased significantly during pregnancy as compared to before and after pregnancy (p < 0.0001). CONCLUSION: In this study, we found no association between dispensing of chloramphenicol eye drops or eye ointment in the first trimester of pregnancy and major congenital malformations. This is in accordance with a previous study analysing the risk of systemic chloramphenicol.