Stela Vujosevic

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.

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.

Retinal layers changes in human preclinical and early clinical diabetic retinopathy support early retinal neuronal and müller cells alterations

Purpose. To evaluate the changes in thickness of individual inner and outer macular and peripapillary retinal layers in diabetes. Methods. 124 subjects (124 eyes) were enrolled: 74 diabetics and 50 controls. Macular edema, proliferative diabetic retinopathy (DR), any intraocular treatment and refractive error >6 diopters were the main exclusion criteria. Full ophthalmic examination, stereoscopic fundus photography, and spectral domain-OCT were performed. After automatic retinal segmentation (layering) in 5 layers, the thickness of each layer was calculated, and values compared among groups. Results. Thirty patients had no DR, 44 patients had non proliferative DR. A significant increase of inner plexiform and nuclear layers was found in DR eyes versus controls (P < 0.001). A significant decrease (P < 0.01) of retinal nerve fiber layer (RNFL) and at specific sites of retinal ganglion cell layer (P = 0.02) was documented in the macula. In the peripapillary area there were no differences between diabetics and controls. Conclusions. Decreased RNFL thickness and increased INL/OPL thickness in diabetics without DR or with initial DR suggest early alterations in the inner retina. On the contrary, the outer retina seems not to be affected at early stages of DM. Automatic intraretinal layering by SD-OCT may be a useful tool to diagnose and monitor early intraretinal changes in DR.

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.

Normal Values for Fundus Perimetry with the Microperimeter MP1

PURPOSE To identify age-stratified normal light sensitivity values for microperimetry (fundus perimetry) and to evaluate the short-term repeatability of the MP1 microperimeter in normal volunteers. DESIGN Multicenter, prospective, observational study. PARTICIPANTS One hundred ninety subjects. METHODS One hundred ninety eyes of 190 healthy volunteers (age range, 20-75 years) underwent automatic, full-threshold microperimetry of the central field (20 x 20 degrees, 77 stimulated points) with the MP1 microperimeter (Nidek Technologies, Gamagori, Japan). Fixation was documented simultaneously. A subgroup of 10 subjects was retested after 1 hour and 1 week to determine the repeatability of this technique. MAIN OUTCOME MEASURES By linear regression analyses, light sensitivity values were obtained from 4 fundus areas and were analyzed for differences related to region, age, and, in a subset of subjects, repeat testing over time and right and left eye variability. Short-term repeatability for each area was evaluated by calculating intraclass correlation coefficients. RESULTS Linear regression analysis showed a significantly greater (P<0.0001) mean macular sensitivity of 19.6+/-0.5 dB in the 20 to 29 years of age group compared with 18.6+/-1.5 dB in the oldest age group of 70 to 75 years. These results were confirmed by the fifth percentile of light sensitivity threshold distribution. Normal and 95% confidence interval age-stratified values were calculated. When results for all 190 subjects were analyzed by region, the superior retinal sector showed significantly lower mean sensitivity values than other sectors (P<0.01, Bonferroni test). In a subset of 10 subjects, repeatability of the test performed at 3 separate visits showed consistent values over time in all areas (P<0.01, intraclass correlation coefficients). CONCLUSIONS Automatic fundus perimetry with the MP1 microperimeter allows for an accurate, repeatable, topographically specific examination of the retinal threshold in selected retinal areas. These findings are the first extensive database of age-related, normal MP1 microperimetry results available to clinicians.

In vivo detection of monosomy 3 in eyes with medium-sized uveal melanoma using transscleral fine needle aspiration biopsy.

Purpose Cytogenetic prognostication of choroidal melanoma, particularly monosomy 3 detections, is limited to enucleated eyes or resected tumors. The authors developed an in vivo technique to detect monosomy 3 using transscleral fine needle aspiration biopsy (FNAB). Methods Eight eyes with medium-sized choroidal melanoma were included in this prospective study. A 25-gauge transscleral FNAB was performed during surgical procedure for brachytherapy, just before applying the radioactive plaque over the tumor base. Sampled material underwent fluorescence in situ hybridization (FISH) with centromeric probes for chromosome 3. Follow-up was >12 months. Results Transscleral FNAB yielded sufficient material in 7 of 8 eyes (87.5 %). Five of seven eyes had monosomy 3. No early or late complications were detected. Conclusions This study demonstrates that medium choroidal melanomas may be safely sampled by intraoperative transscleral FNAB to detect monosomy 3 in vivo.

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.