Purpose
To evaluate changes of specific retinal imaging biomarkers intraretinal hyper‐reflective retinal spots: HRS ; subfoveal neuroretinal detachment: SND; and increased foveal autofluorescence: ...IFAF after intravitreal steroid or anti‐vascular endothelial growth factor treatment in diabetic macular oedema (DME) as possible indicators of retinal inflammatory condition.
Methods
Retrospective analysis of images and clinical charts of 49 eyes (49 patients) with DME treated with intravitreal dexamethasone (dexamethasone, 23 eyes) or intravitreal ranibizumab (ranibizumab, 26 eyes). All patients had fundus colour photograph, spectral domain optical coherence tomography (SD OCT) and fundus autofluorescence (FAF), best‐corrected visual acuity (BCVA) and microperimetry recorded before and 1 month after the end of treatment. Central macular thickness (CMT), number of HRS and presence of SND were evaluated by SD OCT. Fundus autofluorescence images were evaluated for area of (IFAF). Retinal sensitivity within 4° and 12° from fovea was quantified by microperimetry. Changes in morphologic and functional parameters were assessed, and correlation was performed by Pearson's correlation.
Results
Best‐corrected visual acuity and CMT improved in all patients, (p < 0.05, for both groups). Mean number of HRS decreased after both treatments (p < 0.0001). Subfoveal neuroretinal detachment resolved in 85.7% dexamethasone‐treated eyes (p = 0.014) and in 50% ranibizumab‐treated eyes (p = 0.025). Mean IFAF area decreased in both groups, (p < 0.0001, for both). A significantly higher decrease in CMT was observed in dexamethasone‐ versus ranibizumab‐treated eyes, (p = 0.032). In dexamethasone group, higher number of HRS at baseline and larger IFAF were correlated with higher increase in retinal sensitivity; eyes with SND at baseline had major decrease in CMT versus those without SND, (p = 0.003).
Conclusion
Higher number of HRS, larger area of IFAF and presence of SND may indicate a prevalent inflammatory condition in DME with specific response to targeted treatment.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
To evaluate the changes in activity of biomarkers of MuCombining Diaeresisller cells (MC) in aqueous humor of patients with diabetic macular edema after subthreshold micropulse laser, over 1 year.
...Patients with untreated diabetic macular edema and central retinal thickness ≤ 400 μm were enrolled. Best-corrected visual acuity, full ophthalmic examination, and optical coherence tomography were performed. Subthreshold micropulse laser was applied every 3 months. Glial fibrillary acidic protein and inwardly rectifying potassium channel (Kir 4.1), MC activity markers, and vascular endothelial growth factor were quantified in the aqueous humor collected at baseline and at 1, 3, and 12 months after laser. Changes in the macular thickness and inner nuclear layer thickness, where MC bodies are located, were measured.
Ten eyes of 10 patients were included. Best-corrected visual acuity improved at 3 months (P = 0.047) and remained stable. Inner nuclear layer thickness significantly reduced at 12 months (P = 0.012). Glial fibrillary acidic protein, Kir 4.1, and vascular endothelial growth factor decreased at 1 and/or 3 and/or 12 months compared with baseline (P < 0.05).
Subthreshold micropulse laser improves visual function in diabetic macular edema. Kir 4.1 and glial fibrillary acidic protein decrease and inner nuclear layer thickness reduction demonstrate that subthreshold micropulse laser may restore MC function. Subthreshold micropulse laser also reduces vascular endothelial growth factor concentration. The effect of subthreshold micropulse laser in diabetic macular edema may in part be due to changes of MC metabolic activity.
To prospectively analyse microperimetry, standard short-wavelength fundus autofluorescent (SW-FAF) and near infrared-wavelength FAF (NIR-FAF) changes in eyes with geographic atrophy (GA) secondary to ...age-related macular degeneration.
Twenty consecutive eyes (14 patients) affected by GA were enrolled. Repeated microperimetric examinations and FAF images were obtained over a mean follow-up period of 12.3±4.5 months.
GA area was always wider on NIR-FAF versus SW-FAF images (5.05±2.40 mm(2) vs 4.45±2.41 mm(2), p=0.005 baseline; 5.78±2.87 mm(2) vs 5.21±2.77 mm(2), p<0.0001 follow-up). Mean retinal sensitivity significantly decreased during follow-up from 7.68±3.92 dB to 6.71±4.37 dB (p=0.0013). 47.3% of the relative dense scotomas (≤5 dB) progressed to dense scotoma (0 dB). Retinal areas showing relative dense scotoma and characterised by hypo-SW-FAF or hyper-NIR-FAF at baseline had a higher risk of evolving to dense scotoma compared with normo-FAF and hyper-FAF on SW-FAF (OR=2.62 and 2.77, respectively), or normo-FAF at NIR-FAF (OR=2.96).
SW-FAF, compared with NIR-FAF, underestimates GA area at baseline and at follow-up. The enlargement rate of progression based on NIR-FAF is not greater than on SW-FAF. Different SW-FAF and NIR-FAF patterns show different relative risk of progression from relative to dense scotoma. Microperimetry, SW-FAF and NIR-FAF should be combined to obtain adequate morphological and functional prospective information.
To review the most important metabolic effects and clinical safety data of subthreshold micropulse diode laser (D-MPL) in diabetic macular edema (DME).
Review of the literature about the mechanisms ...of action and role of D-MPL in DME.
The MPL treatment does not damage the retina and is selectively absorbed by the retinal pigment epithelium (RPE). MPL stimulates secretion of different protective cytokines by the RPE. No visible laser spots on the retina were noted on any fundus image modality in different studies, and there were no changes of the outer retina integrity. Mean central retinal sensitivity (RS) increased in subthreshold micropulse diode laser group compared to standard ETDRS photocoagulation group.
MPL is a new, promising treatment option in DME, with both infrared and yellow wavelengths using the less aggressive duty cycle (5%) and fixed power parameters. It appears to be safe from morphologic and functional point of view in mild center involving DME.
A pilot prospective, interventional study has been conducted on 10 patients with diabetic macular edema (DME) treated with subthreshold micropulse laser (SMPL) to evaluate changes of individual ...retinal layers and to correlate with functional changes. All patients underwent complete ophthalmologic evaluation including spectral-domain optical coherence tomography (OCT) and microperimetry at baseline, 3 months, 6 months, 9 months, and 12 months. Compared with baseline, a significant decrease was found in inner nuclear layer (INL) and outer retinal layer (ORL) thickness in the central 1 mm (P < .05). Increase in best-corrected visual acuity was significantly and inversely correlated to central retinal thickness (CRT) (P = .0027), INL (P = .0167), and outer nuclear layer (ONL) thickness (P = .0107). Increase in retinal sensitivity was significantly and inversely correlated to CRT and ONL thickness (P < .01). Therefore, SMPL showed to improve firstly functional parameters and then morphologic parameters. Functional parameters were inversely correlated to CRT, INL, and ONL thickness. The exact mechanism of reduction of INL thickness induced by SMPL remains to be further evaluated. Ophthalmic Surg Lasers Imaging Retina. 2018;49:e218-e225..
Abstract Objective To analyze correlation among microperimetry, inner and outer retinal layers, and fundus autofluorescence (FAF) changes in eyes with progressing geographic atrophy (GA) secondary to ...age-related macular degeneration. Methods Microperimetry, spectral-domain optical coherence tomography (SD-OCT), standard short-wavelength FAF (SW-FAF), and near-infrared-wavelength FAF (NIR-FAF) were performed for all patients at both baseline and follow-up visits. FAF pattern, integrity of photoreceptor inner segment/outer segment (IS/OS) junction, total retinal thickness (RT), inner retinal layers (IRL), and outer retinal layers (ORL) thickness changes of every microperimetry extrafoveal tested point were analyzed. Results A total of 366 microperimetry tested points were analyzed (6 patients, 7 eyes). Mean retinal sensitivity significantly decreased ( p = 0.0149), and the percentage of dense scotomas significantly increased ( p = 0.0125). Mean RT and mean ORL thickness significantly decreased (both p < 0.0001). Mean IRL thickness significantly increased ( p = 0.0001). The decrease of ORL thickness was inversely correlated to the IRL thinning (rho = –0.710). FAF pattern at baseline was correlated to RT and ORL thickness (both p < 0.0001) and was significantly correlated to the risk to evolve to dense scotoma during follow-up ( p = 0.0001 at SW-FAF, p < 0.0001 at NIR-FAF). Tested points showing at baseline the loss of photoreceptor IS/OS junction had a greater risk for evolving to dense scotoma compared with those with intact photoreceptor IS/OS junction (odds ratio 3.56, 95% CI 2.41–5.27). Conclusions Retinal sensitivity changes are correlated to IRL and ORL thickness changes, and to photoreceptor IS/OS junction integrity. FAF patterns remain a relevant factor in predicting GA evolution. Microperimetry, SW-FAF and NIR-FAF, and SD-OCT should be combined to obtain adequate morphologic and functional prospective information.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Objective To compare static (during a pure fixation task) versus dynamic (during microperimetry) quantification of fixation stability using microperimetry in normal and pathologic eyes, by ...means of 2 available (clinical and bivariate contour ellipse area BCEA) classification methods. Design Prospective comparative observational study. Participants One hundred and forty-nine eyes (110 patients) with different macular diseases and 171 normal eyes (109 subjects). Methods In all eyes studied, fixation stability was acquired during an isolated fixation task (static fixation) and during microperimetry (dynamic fixation). All fixation data were analyzed and compared by means of a clinical classification and by means of BCEA quantification. Results Pathologic eyes were classified as follows: 41 eyes with diabetic macular edema (DME group), 13 eyes with vitreoretinal interface disease, 60 eyes with age-related macular degeneration (AMD group), and 35 eyes with primary open-angle glaucoma. Fixation stability was not uniform among groups according to clinical classification in both static and dynamic modalities ( p < 0.0001). AMD group showed larger BCEA areas compared with all other groups ( p < 0.0001). All pathologic groups showed more unstable fixation in dynamic fashion according to both clinical and BCEA methods ( p < 0.0001). The variation of fixation stability of control group in dynamic task was highlighted only by BCEA analysis ( p < 0.0001). A deterioration of retinal fixation according to clinical method matches a significant increase in BCEA areas ( p < 0.0001). Conclusions The detection of clinical fixation stability changes improves when acquired in the dynamic modality. BCEA analysis provides more accurate evaluation of fixation stability and may detect minimal quantitative changes of the fixation area. However, a standard clinical classification can also detect changes in fixation stability in pathologic eyes. Both methods are useful tools in the evaluation of fixation stability.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
To assess specific morphologic and functional characteristics in eyes with diabetic macular edema (DME) with subfoveal neuroretinal detachment (SND+) vs DME without SND (SND−).
Cross-sectional, ...prospective, comparative case series.
Seventy-two patients (72 eyes: 22 eyes SND+ and 50 eyes SND−) with treatment-naïve, center-involving DME were evaluated. Data gathering included fundus color photographs, fluorescein angiography, spectral-domain optical coherence tomography (SD-OCT), best-corrected visual acuity (BCVA), and microperimetry. The following parameters were evaluated with SD-OCT: central macular thickness (CMT including SND); central retinal thickness (CRT excluding SND); choroidal thickness (CT); nasal and temporal retinal thickness (RT) at 500 μm and 1500 μm from the fovea; the number of hyperreflective retinal spots (HRS) in the central 3000 μm; and the presence of SND and integrity of the external limiting membrane (ELM). Retinal sensitivity (RS) was evaluated within 4 degrees and 12 degrees of the fovea. Correlation among CT, RS, and HRS in patients with and without SND was determined.
CMT (P = .032), temporal RT at 1500 μm (P = .03), mean CT (P = .009), and mean number of HRS (P = .0001) were all higher in SND+ vs SND− eyes. CRT, BCVA, HbA1c, and prevalence of systemic arterial hypertension were not different between the 2 groups. RS within 4 degrees (P = .002) and 12 degrees (P = .015) was lower in SND+ vs SND− eyes. SND correlated significantly with disruption of the ELM (54.55% vs 24%, P = .01) and lower RS. A direct correlation was found between the number of HRS, presence of SND, CT, and RS within 12 degrees in SND− eyes, and an inverse correlation was found between CT and RS within 12degrees in SND+ eyes.
These data may improve characterization of DME in eyes with SND. DME with SND correlates with greater CT, more HRS, disruption of the ELM, and significant macular functional impairment (RS decrease) vs SND−.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
To evaluate and compare in vivo retinal and choroidal morphologic changes and macular function in patients treated with yellow (Y-MPL) or infrared (IR-MPL) subthreshold micropulse laser in ...center-involving diabetic macular edema.
Prospective, randomized, single institution, comparative 6-month pilot study of 53 eyes (53 patients with diabetes). Inclusion criteria were previously untreated center-involving diabetic macular edema with central retinal thickness ≤400 μm (mild diabetic macular edema). Y-MPL or IR-MPL treatment was performed in a standardized pattern, using in both cases the lowest duty cycle (5%). Morphologic outcomes were the visibility of laser spots (on color fundus photographs COL, fundus autofluorescence, fluorescein angiography, and spectral domain optical coherence tomography), retinal thickness and volume changes, foveal choroidal thickness changes, and integrity and reflectivity of the outer retinal layers. Visual function outcomes were variation in mean 4° and 12° retinal sensitivity and best-corrected visual acuity.
Twenty-six eyes were treated with Y-MPL and 27 eyes with IR-MPL. No visible laser spots on the retina were found on COL, fundus autofluorescence, and fluorescein angiography in both treatment groups at 3 months and 6 months of follow-up. Central retinal thickness, macular volume, foveal choroidal thickness, and best-corrected visual acuity were not significantly different at any follow-up visit between the two treatment groups. There were no changes in the integrity of the external limiting membrane or inner segment/outer segment junction in both treatment groups. Mean central 4° retinal sensitivity increased in both treatment groups at 6 months (P = 0.01 and P = 0.04, respectively). Mean central 12° retinal sensitivity increased in the Y-MPL group only (P = 0.047). But, there was no significant difference in mean 4° and 12° retinal sensitivity between the 2 treatment groups at any follow-up visit.
No clinically visible or invisible scars in the macula were found after Y-MPL or IR-MPL treatment. Both Y-MPL and IR-MPL with the lowest duty cycle (5%) and fixed power parameters seem to be safe from the morphologic and visual function points of view in mild center-involving diabetic macular edema.
The purpose of this study was to evaluate and compare microperimetry and fundus autofluorescence (FAF) after subthreshold micropulse diode laser versus modified Early Treatment Diabetic Retinopathy ...Study photocoagulation for clinically significant diabetic macular edema.
A prospective randomized clinical trial including 62 eyes (50 patients) with untreated, center-involving, clinically significant diabetic macular edema was performed. All patients underwent best-corrected visual acuity determination (logarithm of the minimum angle of resolution), slit-lamp biomicroscopy, FAF, optical coherence tomography, microperimetry (macular sensitivity), and fluorescein angiography before and after treatment. Best-corrected visual acuity, optical coherence tomography, microperimetry, and FAF were repeated at 1-, 3-, 6-, 9-, and 12-month follow-up examinations. Fluorescein angiography was performed at baseline and at 6 and 12 months.
Before treatment, demographic and macular parameters were not different between the two treatment groups. At 12 months, best-corrected visual acuity remained stable in both groups (P = 0.41 and P = 0.82), mean central retinal thickness decreased in both groups (P = 0.0002 and P < 0.0001), and mean central 4 degrees and 12 degrees retinal sensitivity increased in the micropulse diode laser group (P = 0.02 and P = 0.0075) and decreased in the Early Treatment Diabetic Retinopathy Study group (P = 0.2 and P = 0.0026). There was no significant difference in either best-corrected visual acuity or central retinal thickness between the 2 treatment groups (P = 0.48 and P = 0.29), whereas there was a significant difference in 4 degrees and 12 degrees retinal sensitivity (P = 0.04 and P < 0.0001). Fundus autofluorescence never changed in the micropulse diode laser group even after retreatment. In the Early Treatment Diabetic Retinopathy Study group, FAF increased up to 9 months and decreased in 6 eyes (20%) at 12 months.
Micropulse diode laser seems to be as effective as modified Early Treatment Diabetic Retinopathy Study laser photocoagulation in the treatment of clinically significant diabetic macular edema. Micropulse diode laser treatment does not determine any change on FAF showing (at least) nonclinically visible damage of the retinal pigment epithelium. Microperimetry data encourage the use of a new, less aggressive laser therapeutic approach in the treatment of clinically significant diabetic macular edema.
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