Fabiano Cavarzeran

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.

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.

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.

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.

Macular automatic fundus perimetry threshold versus standard perimetry threshold.

Purpose To evaluate if retinal sensitivity threshold obtained with an automatic fundus perimeter may be compared with a standard perimeter retinal threshold. Methods Automatic full-threshold fundus perimetry (microperimetry) of the macular area (10° grid, 37 stimulated points) was quantified with a new automatic fundus perimeter (MP1 microperimeter) in nine normal subjects (18 eyes). Retinal threshold was also quantified using an identical grid projected with a standard Octopus 101 perimeter. Results Mean threshold registered by MP1 microperimeter was 19.7±0.8 dB (range 16–20 dB; 4.38±0.96 asb, range 4–10 asb) versus 33.1±1.7 dB (range 27–38 dB; 0.53±0.22 asb, range 0.16–2 asb) obtained with Octopus perimeter. Mean SD of intraindividual variation was 0.74 dB in MP1 and 1.51 dB in Octopus. No statistically significant differences were documented between right and left eye with both instruments (p=0.64). No reliable mathematical relationship between retinal thresholds could be obtained with the two perimeters. Conclusions Fundus perimetry is a precise, functional fundus-related technique which allows threshold determination at selected retinal points even if fixation is unstable and visual acuity is low. This is beyond the possibility of any static standard perimetry. Normal threshold values obtained with MP1 automatic microperimeter cannot be currently compared with those obtained with standard Octopus perimeter. (Eur J Ophthalmol 2007; 17: 63–8)

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.

HYPERREFLECTIVE RETINAL SPOTS AND VISUAL FUNCTION AFTER ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT IN CENTER-INVOLVING DIABETIC MACULAR EDEMA.

Background: To assess and correlate early modifications in hyperreflective retinal spots (HRS), retinal sensitivity (RS), fixation stability, and best-corrected visual acuity (BCVA) after anti-vascular endothelial growth factor treatment in naive center-involving diabetic macular edema. Methods: Cross-sectional comparative case–control series. Twenty diabetic patients underwent 3 consecutive intravitreal anti-vascular endothelial growth factor injections in the study eye (20 fellow eyes served as control), full ophthalmologic examination including spectral domain optical coherence tomography (Retinascan RS-3000; Nidek, Gamagori, Japan), and microperimetry (MP1; Nidek) at baseline (Visit-V1), 1 month after each injection (V2, V3, V4), and at 6 months (V5). Central retinal thickness, inner and outer retinal thickness, number of HRS, BCVA, RS, and bivariate contour ellipse area were evaluated by analysis of variance test with Bonferroni post hoc test. Correlation analyses were performed by Spearman correlation. Results: In treated eyes, central retinal thickness and inner retinal thickness significantly decreased at V2, V3, V4 versus V1 (P < 0.03 at least for all); the mean number of HRS significantly decreased in both inner and outer retina at all follow-up visits versus V1 (P < 0.008 at least for all); mean RS and bivariate contour ellipse area remained statistically unchanged during the follow-up; BCVA significantly improved at V3, V4, and V5 versus V1 (P = 0.009 at least for all). In fellow eyes, central retinal thickness, HRS, RS, and BCVA did not change at any follow-up. The number of HRS correlated inversely with RS, directly with bivariate contour ellipse area, and not significantly with BCVA. Conclusion: A significant decrease in HRS in the retina after anti-vascular endothelial growth factor treatment is documented. A decrease in HRS correlates with functional parameters, specifically RS. New parameters may be used for treatment evaluation in center-involving diabetic macular edema.

The Prevalence of Age-Related Macular Degeneration in Italy (PAMDI) Study: Report 1

Purpose: The present study aimed to estimate prevalence and risk factors associated with age-related macular degeneration (ARMD) in an Italian population and to analyze differences between urban and rural communities. Methods: We conducted a population-based cross-sectional study among elderly residents in Northeast Italy. Participants were divided into urban and rural groups based on whether they lived in the city of Padova or the villages of Teolo and Torreglia, respectively. Fundus photographs were graded according to the International Classification for Age-related Maculopathy. Results: A total of 1162 randomly selected subjects aged 61 years or more were invited to participate in the study. We examined 885 subjects, and 845 were eligible for fundus photograph grading. ARMD was estimated to affect 62.7% of the whole population (drusen 63–124 μm = 48.3%; drusen ≥125 μm = 10.4%; advanced ARMD = 4.1%). Age was confirmed as a risk factor for drusen ≥125 μm and advanced ARMD (Odds Ratio [OR] = 1.47, 95% Confidence Interval [CI] 1.28–1.69 and OR = 1.62, 95% CI 1.28–2.05, respectively, for a 5-year increase in age). The rural group appeared to be at a higher risk of developing large drusen compared to the urban sample (OR = 1.61, 95% CI 1.01–2.63) when adjusting for age and gender. Conclusions: The results confirmed that ARMD affects a high percentage of the elderly population in Italy. This study does not support the hypothesis that living in a rural environment or belonging to a population of the Mediterranean basin may be protective against the intermediate stages of the disease.