Evelyn Longhin

SUBTHRESHOLD MICROPULSE YELLOW LASER VERSUS SUBTHRESHOLD MICROPULSE INFRARED LASER IN CENTER-INVOLVING DIABETIC MACULAR EDEMA: Morphologic and Functional Safety.

Background: 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. Methods: 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 &mgr;m (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. Results: 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. Conclusion: 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.

Microperimetry, fundus autofluorescence, and retinal layer changes in progressing geographic atrophy

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.

Static and dynamic retinal fixation stability in microperimetry

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.

Subthreshold laser therapy for diabetic macular edema: metabolic and safety issues.

PURPOSE To review the most important metabolic effects and clinical safety data of subthreshold micropulse diode laser (D-MPL) in diabetic macular edema (DME). METHODS Review of the literature about the mechanisms of action and role of D-MPL in DME. RESULTS 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. CONCLUSIONS 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.

Microperimetry Features of Geographic Atrophy Identified With En Face Optical Coherence Tomography.

IMPORTANCE Progressive geographic atrophy (GA) of the retinal pigment epithelium leads to loss of central vision. To identify GA in age-related macular degeneration and assess treatment, correlation of function observed on microperimetry with structure observed on optical coherence tomographic (OCT) images may be of value. OBJECTIVE To characterize the microperimetric function of GA as identified from en face OCT imaging. DESIGN, SETTING, AND PARTICIPANTS In a case-series study, 20 patients (22 eyes) entered the study at the University of Padova according to preplanned conditions. From March 1 to July 30, 2014, en face OCT images were obtained at the outer retinal layer and choroidal layer levels. The microperimetry sensitivity map was superimposed on the en face OCT images, which had been used to measure GA areas. Relative and dense scotoma rates were calculated in the GA areas. After data collection, the study eyes were divided into 3 groups according to the macular residual mean sensitivity. MAIN OUTCOMES AND MEASURES Retinal sensitivity measured by microperimetry within areas of GA identified by en face OCT images. RESULTS Twenty patients (5 men and 15 women) were included in the study, with a mean (SD) age of 79.5 (7.0) years (range, 69-98 years). Macular residual mean retinal sensitivity was less than 5 dB in 7 eyes (group 1), 5 to 10 dB in 9 eyes (group 2), and greater than 10 dB in 6 eyes (group 3). Mean (SD) GA area differed among the groups at the outer retinal (13.13 [5.03] mm2 [range, 5.75-21.04 mm2] in group 1; 7.80 [3.25] mm2 [range, 3.31-13.52 mm2] in group 2; and 3.94 [2.35] mm2 [range, 1.46-7.90 mm2] in group 3; P = .001) and choroidal (11.83 [5.55] mm2 [range, 4.55-22.14 mm2] in group 1; 7.00 [4.29] mm2 [range, 0.90-13.83 mm2] in group 2; and 3.27 [2.29] mm2 [range, 0.91-7.23 mm2] in group 3; P = .007) layer levels. Mean (SD) GA area imaged at the outer retinal layer level was significantly larger than that imaged at the choroidal level in group 3 (difference, 0.67 mm2; 95% CI, 0.31-1.03 mm2; P = .005), but not in groups 1 or 2. Mean (SD) rate of relative scotoma was significantly higher in the GA area imaged at the outer retinal layer level than at the choroidal level in group 3 (47.70% [31.30%] [range, 13.60%-100%] vs 34.00% [37.30%] [range, 0%-100%]; difference, 13.74%; 95% CI, 3.84%-23.63%; P = .02), but not in groups 1 or 2. CONCLUSIONS AND RELEVANCE In the early stage of GA, when retinal sensitivity is relatively good, these data suggest that the GA area imaged on en face OCT at the outer retinal level correctly detects the wide functional degenerative involvement of the photoreceptors. These findings provide novel data that correlate function and structure, which may be of value when assessing treatments that might prevent or reduce the rate of growth of GA.

Repeatability and Reproducibility of Foveal Avascular Zone Area Measurement on Normal Eyes by Different Optical Coherence Tomography Angiography Instruments

Purpose: To compare the foveal avascular zone (FAZ) area measurements produced by different optical coherence tomography angiography (OCTA). Methods: Healthy enrolled volunteers underwent OCTA using 2 different devices: Spectralis HRA+OCTA (Heidelberg Engineering, Heidelberg, Germany) and RS-3000 Advance (Nidek, Gamagori, Japan). Two graders measured FAZ in both superficial (SCP) and deep (DCP) retinal capillary plexuses. The SCP and DCP en face images were visualized automatically segmenting 2 separate slabs defined by the arbitrary segmentation lines created by the software of each OCT device. One grader repeated each measure twice. Results: Fifty-nine eyes were included. The mean FAZ was 0.33 ± 0.09 mm2 at the SCP and 0.57 ± 0.17 mm2 at the DCP measured with RS-3000 versus 0.30 ± 0.08 and 0.35 ± 0.08 mm2, respectively, measured with Spectralis. The measurements of the 2 devices were significantly different (p < 0.0001). The intraoperator agreement was excellent at the SCP (intraclass correlation coefficient, ICC: 0.97 with Spectralis and 0.96 with RS-3000). At the DCP, it was good with Spectralis and fair with RS-3000 (ICC: 0.85 and 0.64, respectively). The interoperator agreement was excellent for Spectralis and good for RS-3000 at the SCP (ICC: 0.97 and 0.93, respectively). It was good at the DCP with both devices (ICC: 0.74 with RS-3000 and 0.81 with Spectralis). Conclusions: FAZ measurements obtained with different OCTA devices differ. These findings should be considered in follow-up studies of patients with retinal vascular diseases.

Early retinal and choroidal OCT and OCT angiography signs of inflammation after uncomplicated cataract surgery

Purpose To evaluate, by means of optical coherence tomography (OCT) and OCT angiography (OCTA), early retinal, choroidal and macular perfusion changes induced by a local inflammatory reaction secondary to uncomplicated cataract surgery. Methods Selected eyes undergoing cataract surgery were enrolled in a prospective study. OCT and OCTA were performed before cataract surgery (T0) and at day: 1 (T1), 7 (T7), 30 (T30) and 90 (T90). Inner (IR) and outer retinal (OR) volumes, choroidal volume, hyper-reflective retinal spots (HRS) in IR and OR changes were measured at OCT. Macular perfusion was analysed in superficial (SCP), intermediate (ICP) and deep retinal capillary plexuses (DCP). Results Nine eyes of nine selected patients were consecutively enrolled. Mean IR volume changed after surgery (p=0.0001), increasing progressively from 4.391±0.231 mm³ at T0 to 4.573±0.241 mm³ at T30, p=0.0002. Both mean OR and choroidal volume increased, mainly at T30, but not significantly (p=0.4360 and p=0.2300, respectively). Mean HRS changed during follow-up, increasing at first in IR and later in OR (at T1 and T7, respectively, both p<0.0001). Macular ICP and DCP perfusion increased at T1, whereas macular SCP perfusion did not change. At T90, all OCT and OCTA parameters had almost reached baseline levels. Conclusions The increase of HRS at first in IR and later in OR seems to confirm their inflammatory nature. Early OCTA changes (underline) underscore a selective susceptibility of DCP and ICP to a localised inflammatory reaction induced by cataract surgery.

Early OCT angiography changes of type 1 CNV in exudative AMD treated with anti-VEGF

Aims To investigate, with optical coherence tomography angiography (OCTA), short-term changes of type 1 choroidal neovascularisation (CNV), secondary to exudative age-related macular degeneration, after anti-vascular endothelial growth factor (VEGF) treatment. Methods Patients affected by type 1 CNV treated with intravitreal anti-VEGF were consecutively enrolled. All patients underwent OCTA examination before and 48 hours after anti-VEGF treatment. Quantitative and qualitative vascular and morphological macular changes were evaluated. Results Sixteen eyes were included (11 treated with aflibercept and 5 with ranibizumab). Both CNV mean area and pigment epithelium detachment significantly reduced (p=0.0004 and p=0.0007, respectively) after treatment. Cystoid macular oedema (four eyes) decreased in all cases. Neuroretinal detachment (13 eyes) decreased in 85% of cases (11 eyes). Fine CNV vessels density decreased in 75% (12 eyes), whereas larger CNV vessels density remained stable in 66.7% (10 eyes), choroidal flow void signal (7 eyes at baseline) increased in 42.9% (3 eyes) of them and remained stable in 57.1% (4 eyes). Interoperator reproducibility for OCT examination was good for all measurements (intraclass correlation coefficient>0.65). Conclusion Early remodelling of type 1 CNV network after treatment may be non-invasively and reproducibly analysed by means of OCTA. Choroidal perfusion impairment, choroidal flow void signal, surrounding CNV may change during treatment.

Rod function in diabetic patients without and with early diabetic retinopathy.

Purpose To compare rod function among diabetic patients without and with mild nonproliferative diabetic retinopathy (DR) and healthy controls by means of scotopic microperimetry and dark-adapted electroretinography. Methods Sixty-one diabetic patients and 30 age-matched controls (control group) underwent complete ophthalmic examination, scotopic microperimetry, and dark-adapted 0.01 electroretinography (DA-ERG). Results In 32 eyes, DR was absent (no-DR group); in 29 eyes, only microaneurysms were observed (DR group). No statistically significant differences in fixation stability, fixation location, or scotopic sensitivity among the 3 groups were observed. Implicit time and amplitude of the DA-ERG b-wave of no-DR and DR groups were not different from controls. Scotopic microperimetry showed a dense scotoma centered onto the fovea in all subjects, consistent with the rod-free zone. Greater scotopic sensitivity was found in a ring located 8° from the fovea (9.33 ± 1.33 dB). Conclusions Diabetic patients without DR and with mild nonproliferative DR did not show alterations in rod-based function, as examined by microperimetry and confirmed by DA-ERG. Scotopic microperimetry measures rod-based function and offers additional information in the evaluation of the aspects of involvement of retinal cells in diabetes.