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.

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.

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.

Twenty years of endophthalmitis: Incidence, aetiology and clinical outcome.

PURPOSE: To review the incidence, aetiology and outcomes of endophthalmitis during a 20-year period in a Norwegian university hospital. METHODS: Single-centre retrospective review. Medical records of all patients admitted to Stavanger University Hospital with suspected endophthalmitis between January 1999 and December 2018 were reviewed. RESULTS: We identified 84 eyes of 81 patients. Postoperative endophthalmitis (PE) was seen in 64 eyes (76%), endogenous endophthalmitis in thirteen eyes (15%), trauma in four eyes (5%) and three eyes (4%) had keratitis-associated endophthalmitis. Administration of intravitreal injections (IVI) was the most common cause (30%), followed by cataract surgery (CS) (21%). Of 40238 IVI, 23 PE cases were identified (incidence, 0.057%; 95% confidence interval [CI] 0.036-0.086%). Of 39697 CS, 12 PE cases were identified (incidence, 0.030%; 95%CI 0.016-0.053%). After introduction of intracameral cefuroxime PE incidence after CS decreased from 0.10% in 1999-2003 to 0.015% in 2004-2018 (p = 0.003). Eighty-four per cent of organisms were Gram-positive. Coagulase-negative staphylococci accounted for 54% of culture-proven cases, and 89% of post-IVI culture-proven cases. Thirty eyes (36%) either regained their previous vision or lost ≤1 Early Treatment Diabetic Retinopathy Study line. One third of endophthalmitis cases had a favourable visual outcome of logMAR 0.2 or better. CONCLUSION: PE after IVI occurred in 1 in 1750 procedures, and was the most common cause of PE. The incidence of PE after CS has decreased >sixfold since 2003, to 1 in 6700 surgeries. A high proportion of low-virulence bacterial species may have contributed to the favourable visual outcome.

Drusenoid pigment epithelial detachment volume is associated with a decrease in best-corrected visual acuity and central retinal thickness: the Norwegian Pigment Epithelial Detachment Study (NORPED) report no. 1.

PURPOSE: To investigate the association of drusenoid pigment epithelial detachment (DPED) volume and change in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) during the growth phase of large DPEDs. METHODS: Patients from an ongoing prospective observational study, the Norwegian Pigment Epithelial Detachment Study (NORPED), with 1 year of follow-up and DPEDs ≥1000 µm in diameter, examined with the Heidelberg Spectralis HRA-OCT were included. Patients with DPEDs in the regression phase were excluded. Multicolour, near-infrared reflectance, optical coherence tomography (OCT) and OCT angiography images were obtained every 6 months. Fluorescein angiography and indocyanine green angiography were performed at baseline and yearly to exclude choroidal neovascularization (CNV). RESULTS: Forty-four patients and 66 eyes were included. In the statistical model for BCVA, every 1.0 mm3 increase in DPED volume led to a decrease in BCVA of 4.0 ETDRS letters (95% CI, -7.0 to -1.0, p = 0.008). A decrease in BCVA was significantly associated with older patient age, the presence of acquired vitelliform lesions and subfoveal location of the DPEDs. In the model for CRT, every 1.0 mm3 increase in DPED volume led to a decrease in CRT of 26.7 µm (95% CI, -44.4 to -9.0, p = 0.003). Two eyes had progression of geographic atrophy and none developed CNV. CONCLUSION: The increasing volume of DPEDs during the growth phase is associated with a decrease in BCVA and CRT. The subfoveal location of DPEDs and the presence of acquired vitelliform lesions appear to be associated with a further reduction in BCVA.