Elisabetta Pilotto

Microperimetry and fundus autofluorescence in patients with early age‐related macular degeneration

Background: Early age-related macular degeneration (AMD) has been correlated with different functional alterations, but the exact relationship between fundus lesions and overlying sensitivity is not well known. The aim of this study was to compare fundus-related sensitivity (microperimetry) and fundus autofluorescence (FAF) of the macular area with drusen and pigment abnormalities in early AMD. Methods: 13 consecutive patients with early AMD and visual acuity of 20/20 were studied by means of microperimetry, which automatically analyses macular light differential threshold and fixation patterns. Fundus colour photo and FAF of the macular area were recorded on the same day. Microperimetry was exactly (topographically) superimposed over FAF images. Results: Macular sensitivity significantly decreased over large drusen (11.2 ± 5.6 dB, p<0.0001) and over pigment abnormalities (13.1 ± 3.6 dB, p<0.0001). When both characteristics were present the reduction was greater if compared with its absence (9.6 ± 4.3 versus 15.0 ± 4.5 dB, p<0.0001). Sensitivitity reduction was significant in areas with altered FAF when compared with areas with normal FAF (p<0.0001). Conclusions: Increased FAF in early AMD has a functional correlate exactly quantified by microperimetry. In retinal areas affected by early AMD retinal sensitivity deteriorates, despite good visual acuity. Microperimetry may allow the early detection of functional impairment caused by these lesions. Both microperimetry and FAF may be useful to monitor AMD progression.

Fixation pattern and macular sensitivity in eyes with subfoveal choroidal neovascularization secondary to age-related macular degeneration. A microperimetry study

Purpose. To investigate the effects of subfoveal choroidal neovascularizzation (CNV) secondary to age-related macular degeneration (AMD) on macular functional parameters quantified with an automatic fundus perimeter. Methods. 118 eyes of 98 consecutive patients with subfoveal CNV secondary to AMD were evaluated. Best corrected visual acuity (ETDRS charts), fundus photography, and fluorescein angiography were performed. Microperimetry (fundus-related perimetry) was used to quantify macular sensitivity and fixation pattern (location and stability). Results. Of 118 eyes: 26 (21.9%) had central, 18 (15.1%) poor central and 74 (63.0%) eccentric fixation; 31 (26.0%) had stable, 42 (35.6%) relatively unstable and 45 (38.4%) unstable fixation. In 75 eyes (63.4%) a dense central scotoma was found. Angiographic classification of subfoveal CNV (occult versus classic) was not significantly related to fixation pattern (location: P = 0.274; stability: P = 0.385), and presence of dense scotoma (P = 0.41). Conclusion. Microperimetric quantification of macular sensitivity and fixation pattern in eyes with subfoveal CNV secondary to AMD offers new data about the impact of visual impairment in these eyes. Moreover, microperimetry improves the functional evaluation of subfoveal CNV in AMD.

Microperimetry And Fundus Autofluorescence In Diabetic Macular Edema: Subthreshold Micropulse Diode Laser Versus Modified Early Treatment Diabetic Retinopathy Study Laser Photocoagulation

Purpose: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. Methods: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. Results: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° and 12° 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° and 12° 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. Discussion: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.

Macular and peripapillary choroidal thickness in diabetic patients

Purpose: To investigate macular and peripapillary choroidal thickness (CT) in diabetic patients with and without diabetic retinopathy (DR). Methods: One hundred and fifty subjects were enrolled: 102 diabetic patients (102 eyes) and 48 normals, as controls. Exclusion criteria were previously treated DR, refractive error higher than ±3 diopters, and treated or untreated glaucoma. All patients underwent full ophthalmic examination, stereoscopic color fundus photography, and spectral domain optical coherence tomography (RS-3000; Nidek). Spectral domain optical coherence tomography examination consisted of linear scans, 6 mm in length, centered onto the fovea, and circle scan positioned around the optic disk (3.46 mm in diameter). Choroidal thickness was measured manually at the fovea and at 1, 2, and 3 mm distance along all scans in the macula. Peripapillary CT was measured at eight points along the circle scan. All measurements were performed independently by 2 masked graders. Results: Mean age was not significantly different between patients with diabetes and controls. In the macular area, CT was significantly lower in the nasal quadrant versus all other quadrants (P < 0.0001), in both groups. In the peripapillary area, CT was significantly lower in the inferior quadrant versus all other quadrants (P < 0.05), in both groups. Mean macular and peripapillary CT progressively and significantly decreased with increasing level of DR (nonproliferative and proliferative DR vs. controls, P < 0.05). No significant CT difference was found between controls and diabetic eyes without detectable DR. Diabetic macular edema did not influence CT. Interobserver coefficient of repeatability was 28.8 (95% confidence interval, 24.8–32.8) for foveal measurements and 13.0 (95% confidence interval, 11.2–14.8) for peripapillary measurements. Pearson correlation coefficient was 0.99, and P <0.0001 for all measurements. Conclusion: Choroidal thickness is reduced in diabetic eyes and parallels appearance and evolution of DR. Spectral domain optical coherence tomography clearly confirms in vivo previously reported histopathologic observations. The role of choroid in the pathophysiology of DR needs to be adequately investigated.

Screening for Diabetic Retinopathy: 1 and 3 Nonmydriatic 45-degree Digital Fundus Photographs vs 7 Standard Early Treatment Diabetic Retinopathy Study Fields

PURPOSE To evaluate if simple- or multiple-field digital color nonmydriatic (NM) retinal images can replace 7 standard stereoscopic fundus photographs in the screening of diabetic retinopathy (DR). DESIGN Prospective, masked, comparative case series. METHODS One hundred and eight eyes of 55 diabetics were studied to determine single lesions and to grade clinical levels of DR and diabetic macular edema (DME) using both 1 and 3 NM digital color retinal images compared with the Early Treatment Diabetic Retinopathy Study (ETDRS) 7 standard 35-mm stereoscopic color fundus photographs (7F-ETDRS). All eyes underwent NM 45-degree field images of 1 central field (1F-NM), NM 45-degree field images of 3 fields (3F-NM), and, after pupil dilatation, 30-degree 7F-ETDRS photography. Images were analyzed by 2 independent, masked retinal specialists (S.V. and E.B.), lesion-by-lesion according to the ETDRS protocol and for clinical severity level of DR and DME according to the international classification of DR. RESULTS Using 7F-ETDRS as the gold standard, agreement was substantial for grading clinical levels of DR and DME (kappa = 0.69 and kappa = 0.75) vs 3F-NM; moderate for DR level (kappa = 0.56) and substantial for DME (kappa = 0.66) vs 1F-NM; almost perfect for detecting presence or absence of DR (kappa = 0.88) vs both 1F-NM and 3F-NM; and almost perfect for presence or absence of DME (kappa = 0.97) vs 3F-NM and substantial (kappa = 0.75) vs 1F-NM. Sensitivity and specificity for detecting referable levels of DR were 82% and 92%, respectively, for 3F-NM and 71% and 96%, respectively, for 1F-NM. CONCLUSIONS Three color 45-degree NM fundus fields may be an effective tool in a screening setting to determine critical levels of DR and DME for prompt specialist referral. One central 45-degree image is sufficient to determine absence or presence of DR and DME, but not for grading it.

Diabetic Macular Edema: Fundus Autofluorescence and Functional Correlations

PURPOSE Diabetic macular edema (DME) shows variable clinical characteristics with unpredictable results to local treatment, probably reflecting different phenotypes. The purpose of this study was to evaluate the role of structural and functional macular imaging in the characterization of DME patterns. METHODS One hundred fifty-one eyes of 92 diabetic patients with untreated clinically significant macular edema (CSME) underwent best corrected visual acuity (BCVA) determination (logMAR), slit lamp biomicroscopy; fluorescein angiography; optical coherence tomography (OCT; mean central retinal thickness [CRT], volume, and DME pattern); fundus autofluorescence (FAF; absent or increased [i]FAF, single or multiple spots; iFAF area quantification); and microperimetry. Linear correlation, data agreement and three-way analysis of covariance were used for statistics. RESULTS Thirty-five (23.2%) eyes had normal FAF; and 116 eyes had iFAF: 48 (31.8%) single-spot iFAF, 68 (45%) multiple-spot iFAF. Retinal sensitivity in areas with iFAF was 11.5±5.3 dB (vs. 15.1±3.9 dB in normal areas, P<0.005). Retinal sensitivity of the central field was 15.1±3.9 dB in normal FAF, 12.4±4.8 dB in single-spot iFAF and 11.4±4.9 dB in multiple-spot iFAF (P<0.05). OCT CRT and volume were not significantly different between the FAF groups. OCT volume correlated to OCT CRT (r=0.68), retinal sensitivity in iFAF (r=-0.50) and BCVA (r=0.42). Cystoid OCT pattern and FA edema patterns correlated with iFAF presence (P<0.0001). CONCLUSIONS In CSME, FAF correlates better with OCT patterns and central field microperimetry rather than with visual acuity. FAF is a rapid, noninvasive technique that may give new insight into the evaluation of DME. The validity of FAF in the follow-up and treatment outcomes in DME remain to be assessed.

Hyperreflective Intraretinal Spots in Diabetics without and with Nonproliferative Diabetic Retinopathy: An In Vivo Study Using Spectral Domain OCT

Purpose. To evaluate the presence of hyperreflective spots (HRS) in diabetic patients without clinically detectable retinopathy (no DR) or with nonproliferative mild to moderate retinopathy (DR) without macular edema, and compare the results to controls. Methods. 36 subjects were enrolled: 12 with no DR, 12 with DR, and 12 normal subjects who served as controls. All studied subjects underwent full ophthalmologic examination and spectral domain optical coherence tomography (SD-OCT). SD-OCT images were analyzed to measure and localize HRS. Each image was analyzed by two independent, masked examiners. Results. The number of HRS was significantly higher in both diabetics without and with retinopathy versus controls (P < 0.05) and in diabetics with retinopathy versus diabetics without retinopathy (P < 0.05). The HRS were mainly located in the inner retina layers (inner limiting membrane, ganglion cell layer, and inner nuclear layer). The intraobserver and interobserver agreement was almost perfect (κ > 0.9). Conclusions. SD-OCT hyperreflective spots are present in diabetic eyes even when clinical retinopathy is undetectable. Their number increases with progressing retinopathy. Initially, HRS are mainly located in the inner retina, where the resident microglia is present. With progressing retinopathy, HRS reach the outer retinal layer. HRS may represent a surrogate of microglial activation in diabetic retina.

Fundus autofluorescence and microperimetry in progressing geographic atrophy secondary to age-related macular degeneration

Purpose 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. Methods 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. Results GA area was always wider on NIR-FAF versus SW-FAF images (5.05±2.40 mm2 vs 4.45±2.41 mm2, p=0.005 baseline; 5.78±2.87 mm2 vs 5.21±2.77 mm2, 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). Conclusions 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.

Retinal fixation impairment in diabetic macular edema.

Purpose: To evaluate the characteristics of retinal fixation in patients with diabetic macular edema using microperimetry. Methods: One hundred seventy nine eyes (98 patients) with untreated diabetic macular edema underwent best corrected visual acuity determination (Early Treatment Diabetic Retinopathy Study charts), digital color stereoscopic fundus photos, fluorescein angiography and Optical Coherence Tomography assessment of macula. Fixation and retinal thresholds were determined with an automatic microperimeter. Results: Best corrected visual acuity (approximate Snellen equivalent) was: 20/25 or better in 90 (52%) eyes, 20/50 to 20/32 in 39 (22.5%) eyes, 20/200 to 20/62.5 in 35 (20.2%) eyes and inferior to 20/200 in 9 (5.2%) eyes. Fixation was central in 128(71.51%), poor central in 26(14.53%) and predominantly eccentric in 25(13.97%) eyes; stable in 133(74.3%), relatively unstable in 42(23.46%) and unstable in 4(2.23%) eyes. Both fixation location and stability were not significantly influenced by edema characteristics (diffuse, focal, cystoid, spongelike, with or without subfoveal neuroretinal detachment), (P > 0.05), whereas they were significantly influenced by the presence of subfoveal hard exudates, (P = 0.004 and P = 0.0046, respectively). Site and stability of fixation were significantly associated, (P < 0.0001). Retinal pseudofovea would have been covered by laser photocoagulation in 24(47%) eyes with poorly central and predominantly eccentric fixation and in 29(63%) eyes with relatively unstable and unstable fixation. Conclusion: Microperimetry shows that fixation location and stability in patients with diabetic macular edema are independent of edema characteristics, except when subfoveal hard exudates are present. Location of pseudofovea may influence treatment strategy.

Short wavelength fundus autofluorescence versus near-infrared fundus autofluorescence, with microperimetric correspondence, in patients with geographic atrophy due to age-related macular degeneration

Aim To compare standard short-wavelength fundus autofluorescence (SW-FAF) and near infrared-wavelength fundus autofluorescence (NIR-FAF) in detecting geographic atrophy (GA) secondary to age-related macular degeneration, and its retinal sensitivity impairment. Methods Twenty-five consecutive patients (36 eyes) affected by GA were studied by means of fundus autofluorescence imaging, using both SW-FAF (excitation: 488 nm, emission >500 nm) and NIR-FAF (excitation: 787 nm, emission >800 nm). All patients underwent microperimetry to assess fixation characteristics and retinal sensitivity. Results In the extrafoveal region, the total hypoautofluorescent (hypo-FAF) area was significantly wider with NIR-FAF than with SW-FAF (8.03±6.68 mm2 vs 7.37±6.34 mm2 respectively; p=0.005). In the foveal area, the total hypo-FAF area was smaller with NIR-FAF than with SW-FAF (0.19±0.03 mm2 versus 0.42±0.12 mm2 respectively; p=0.008). Foveal sparing was larger at NIR-FAF compared with SW-FAF (p=0.021). In nine cases (25%) the site of fixation was hypoautofluorescent on SW-FAF, but normal on NIR-FAF with preserved retinal sensitivity. Conclusions Standard SW-FAF may overestimate GA in the foveal area, correctly detected by NIR-FAF. In the extrafoveal area, SW-FAF may underestimate GA. Standard SW-FAF should be integrated with NIR FAF when detecting and following GA to avoid inconsistent results and misinterpretation, from both a morphological and functional perspective. Microperimetry helps to quantify retinal sensitivity in GA.