Search

This cross-sectional study evaluated the relationship between 1 ) functional and structural measurements of neurodegeneration in the initial stages of diabetic retinopathy (DR) and 2 ) the presence of neurodegeneration and early microvascular impairment. We analyzed baseline data of 449 patients with type 2 diabetes enrolled in the European Consortium for the Early Treatment of Diabetic Retinopathy (EUROCONDOR) study (NCT01726075). Functional studies by multifocal electroretinography (mfERG) evaluated neurodysfunction, and structural measurements using spectral domain optical coherence tomography (SD-OCT) evaluated neurodegeneration. The mfERG P1 amplitude was more sensitive than the P1 implicit time and was lower in patients with Early Treatment of Diabetic Retinopathy Study (ETDRS) level 20-35 than in patients with ETDRS level <20 ( P = 0.005). In 58% of patients, mfERG abnormalities were present in the absence of visible retinopathy. Correspondence between SD-OCT thinning and mfERG abnormalities was shown in 67% of the eyes with ETDRS <20 and in 83% of the eyes with ETDRS level 20-35. Notably, 32% of patients with ETDRS 20-35 presented no abnormalities in mfERG or SD-OCT. We conclude that there is a link between mfERG and SD-OCT measurements that increases with the presence of microvascular impairment. However, a significant proportion of patients in our particular study population (ETDRS ≤35) had normal ganglion cell-inner plexiform layer thickness and normal mfERG findings. We raise the hypothesis that neurodegeneration may play a role in the pathogenesis of DR in many but not in all patients with type 2 diabetes., (© 2017 by the American Diabetes Association.)

Purpose: To analyze the individual value and the contribution of color fundus photography (CFP) and optical coherence tomography (OCT) in the screening of age-related macular degeneration (AMD) of an unselected population. Methods: CFP and OCT images of 15957 eyes of 8069 subjects older than 55 years, obtained during a population-based screening for AMD using a single diagnostic non-mydriatic imaging device, were analyzed by a blinded examiner. The two techniques were preliminary evaluated considering the dichotomous parameter "gradable/ungradable", then gradable images were classified. CFP were graded according to the standardized classification of AMD lesions. OCT images were also categorized considering the presence of signs of early/intermediate AMD, late AMD, or other retinal diseases. Another blinded operator re-graded 1978 randomly selected images (for both CFP and OCT), to assess test reproducibility. Results: Of the 15957 eyes, 8356 CFP (52.4%) and 15594 (97.7%) OCT scans were gradable. Moreover, most of the eyes with ungradable CFP (7339, 96.6%) were gradable at OCT. AMD signs were revealed in 7.4% of gradable CFP and in 10.4% of gradable OCT images. Moreover, at OCT, AMD signs were found in 1110 (6.9%) eyes whose CFP were ungradable or without AMD (847 and 263 eyes, respectively). The inter-operator agreement was good for the gradable versus ungradable parameter, and optimal for the AMD grading parameter of CFP. The agreement was optimal for all OCT parameters. Conclusions: OCT provided gradable images in almost all examined eyes, compared to limited CFP efficiency. Moreover, OCT images allowed to detect more AMD eyes compared to gradable photos. OCT imaging appears to significantly improve the power of AMD screening in a general, unselected population, compared to CFP alone. [ABSTRACT FROM AUTHOR]

Purpose: To better understand the pathophysiology of geographic atrophy (GA), secondary to age-related macular degeneration, eyes affected by unilateral GA (and CNV in the fellow eye; U-GA group) or by bilateral GA (B-GA group) were evaluated using an integrated morpho-functional approach and quantifying biomarker of retinal macroglial activity. Methods: Patients with U-GA and B-GA and foveal-sparing were consecutively enrolled in a prospective study. All included eyes underwent fundus photography, fundus autofluorescence (FAF), foveal retinal and choroidal thicknesses (RT, CT), contrast sensitivity, best-corrected visual acuity (BCVA), low-luminance VA (LLVA) and low-luminance deficit (LLD), and mesopic and scotopic microperimetry and multifocal electroretinography (mfERG). Glial fibrillary acidic protein (GFAP), biomarker of Müller cell activation, was quantified in the aqueous humor (AH). Results: Forty eyes of 40 patients (18 in the U-GA group and 22 in the B-GA group) were studied. RT, GA area, BCVA, contrast sensitivity, mfERG, and microperimetry (at both background luminances) were not different between groups. CT was significantly thinner in U-GA compared to B-GA group (p = 0.020). Both LLVA and LLD were significantly worse in the B-GA vs U-GA group (p = 0.033 and p = 0.048, respectively). GFAP intraocular concentration was significantly higher in the B-GA group (p = 0.01). Conclusions: Different pathophysiologic mechanisms may be responsible for GA in unilateral (with CNV in the fellow eye) compared to bilateral GA cases. In unilateral cases, a thinner choroid seems to play a key role. Whereas, in bilateral cases, Müller cells and their supported photoreceptors may be primarily involved. [ABSTRACT FROM AUTHOR]

Purpose. To report the impact of baseline central retinal thickness (CRT) on outcomes in patients with diabetic macular edema (DME) in VIVID-DME and VISTA-DME. Methods. Post hoc analyses of two randomized controlled trials in which 862 DME patients were randomized 1 : 1 : 1 to treatment with intravitreal aflibercept 2.0 mg every 4 weeks (2q4), intravitreal aflibercept 2.0 mg every 8 weeks after five initial monthly doses (2q8), or macular laser photocoagulation at baseline and as needed. We compared visual and anatomical outcomes in subgroups of patients with baseline CRT < 400 μm and ≥400 μm. Results. At weeks 52 and 100, outcomes with intravitreal aflibercept 2q4 and 2q8 were superior to those in laser control-treated patients regardless of baseline CRT. When looked at in a binary fashion, the treatment effect of intravitreal aflibercept versus laser was not significantly better in the ≥400 μm than the <400 μm group; when looked at as a continuous variable, baseline CRT seemed to have an impact on the treatment effect of intravitreal aflibercept versus laser. Conclusions. Post hoc analyses of VIVID-DME and VISTA-DME demonstrated the benefits of intravitreal aflibercept treatment in DME patients with baseline CRT < 400 μm and ≥400 μm. This trial is registered with NCT01331681 and NCT01363440. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate functional changes (retinal sensitivity and fixation characteristics) determined by microperimetry in patients with early and intermediate AMD over 6 years. Methods: Prospective, longitudinal follow-up (FU) study of 16 patients (29 eyes) with early and intermediate AMD (AREDS 2 and AREDS 3 classification). All eyes underwent: complete ophthalmic examination with best corrected visual acuity (BCVA) determination, color fundus photo (CFP), optical coherence tomography and microperimetry. All CFP were evaluated by two retinal specialists masked to functional data for changes in severity of clinical features over the course of FU. Results: Of 17 eyes graded as AREDS 2 at baseline, 14 (82.35 %) remained stable, and 3 (18.75 %) progressed to AREDS 3. Of 12 eyes graded as AREDS 3 at baseline, 10 remained stable (83.33 %), and 2 (16.67 %) progressed to AREDS 4. Mean BCVA significantly deteriorated in both AREDS 2 ( p = 0.006) and AREDS 3 ( p = 0.016), with greater decrease in AREDS 3 ( p = 0.01)6. Mean retinal sensitivity (RS) significantly decreased over time in both AREDS 2 ( p < 0.0001) and AREDS 3 grou p ( p = 0.002), with greater decrease in AREDS 3 ( p = 0.006). The mean number of dense scotomas did not change in AREDS 2 ( p = 0.3), but significantly increased in the AREDS 3 group ( p = 0.035). Points with decreased RS were located in all but the central point ( p < 0.0001 for all), without significant differences in number among rings. In the AREDS 2 group, fixation stability remained unchanged. In the AREDS 3 group, four eyes deteriorated from stable to unstable fixation at FU ( p = 0.045). Conclusion: A significant deterioration in RS is reported in early and intermediate AMD eyes, whereas fixation stability changed only in intermediate AMD (AREDS 3) over long-term follow-up. Microperimetry examination can become a new functional biomarker in early and intermediate AMD patients. [ABSTRACT FROM AUTHOR]

Purpose To prospectively analyse microperimetry, standard short-wavelength fundus autofluorescent (SWFAF) 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. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the ability of confocal scanning laser ophthalmoscope (cSLO) in the retromode imaging modality in detecting retinal changes secondary to exudative age-related macular degeneration (AMD). Methods: Seventeen eyes of 13 consecutive patients affected by CNV secondary to AMD were evaluated with optical coherence tomography (OCT) to detect neuroretinal detachment (NRD), pigment epithelial detachment (PED), cystoid macular edema (CME), and epiretinal membranes (ERM). All eyes were examined with a cSLO equipped with infrared retromode (RM) imaging modality. Infrared and fundus autofluorescence images were also obtained (IR and FAF). The intermethod agreement between OCT and cSLO was evaluated considering single cSLO imaging modality separately (IR, FAF, and RM), and all imaging modalities together. Results: Eight eyes (47 %) had NRD at OCT; intermethod agreement was poor for any single cSLO imaging modality considered separately ( k: 0.14, 0.01, and 0.29 for cSLO IR, FAF, and RM, respectively). Four eyes had PED at OCT (24 %); intermethod agreement was mild for cSLO RM, poor for IR and FAF ( k: 0.51, 0.16, and 0.00, respectively). CME was present in eight eyes (47 %); intermethod agreement was excellent for cSLO RM, poor for IR and FAF ( k: 0.88, 0.38, and 0.26, respectively). ERM was present in three eyes (18 %); intermethod agreement was mild for cSLO IR, poor for FAF, and excellent for RM ( k: 0.59, 0.00, and 0.76, respectively). Conclusions: cSLO RM imaging is a useful and reproducible technique in detecting retinal features associated with CNV, particularly CME. [ABSTRACT FROM AUTHOR]

. Purpose: To determine the validity of scanning laser ophthalmoscopy in the retromode (RM-SLO) versus other imaging modalities in the diagnosis of diabetic macular oedema (DME). Methods: Two hundred and sixty-three eyes were examined. Inclusion criteria were any stage of untreated or treated diabetic retinopathy and four imaging modalities of the macula carried out on the same day: time domain optical coherence tomography (OCT), fundus autofluorescence (FAF), RM-SLO and fluorescein angiography (FA). Two masked retinal specialists independently graded all images. Agreement between RM-SLO and OCT, FA and FAF in evaluating the presence and patterns of DME was evaluated by kappa statistics, sensitivity, specificity, observed proportional agreement, and proportional agreement in positive and negative cases. Results: The agreement in evaluating the presence/absence of DME between RM-SLO and OCT, FA and FAF was good: κ = 0.73 (confidence interval; CI, 0.64-0.83), κ = 0.71 (CI, 0.61-0.81) and κ = 0.73 (CI, 0.63-0.83), respectively. The agreement in evaluating cystoid pattern of DME was almost perfect between RM-SLO and OCT, RM-SLO and FA, κ > 0.8; and good between RM-SLO and FAF, κ > 0.7. The agreement in evaluating the presence/absence of subfoveal neuroretinal was almost perfect between RM-SLO and OCT (κ = 0.83; 95% CI, 0.70-0.96). Subfoveal neuroretinal detachment did not show any specific pattern on FA or FAF. Sensitivity and specificity of RM-SLO in evaluating DME was 97.7% and 71.9% versus OCT, 97.4% and 68.1% versus FA and 96.1% and 73.3% versus FAF. Retinal thickness of 233 μm represented the cut-off value to define DME by RM-SLO. Conclusions: The combined use of non-invasive imaging techniques can improve the diagnostic interpretation of different aspects of DME. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose. To describe the long term outcome of patients with subfoveal, occult choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) treated with subthreshold transpupillary thermotherapy. Methods. 82 eyes of 82 consecutive patients with subfoveal occult CNV secondary to AMD were treated with subthreshold transpupillary thermotherapy. Best corrected visual acuity, fundus photography, fluorescein and indocyanine green angiography were performed. Results. All patients have been followed for at least 24 months. At the final follow-up visit, 75.6% of patients had stable or improved visual acuity and 24.4% had worsened visual acuity. No overtreatment side effects were found. Conclusion. Subthreshold transpupillary thermotherapy seems effective in stabilizing visual acuity in patients affected by occult, subfoveal CNV even on a long-term basis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 (20×20°, 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. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. [Copyright &y& Elsevier]

Purpose: To report angiographic observations about feeder vessel identification after photodynamic therapy in patients with choroidal neovascularization caused by age-related macular degeneration.Design: Cohort study.Methods: We analyzed fluorescein and indocyanine green dynamic angiography in 156 eyes of 145 patients before and after photodynamic therapy to identify the feeder vessels of the choroidal neovascular membrane.Results: Before photodynamic therapy one or more feeder vessel could be detected in 35 (22.4%) out of 156 eyes with choroidal neovascularization. Three months after photodynamic therapy, a feeder vessel could be identified in 112 (84.2%) out of 133 eyes with persistent choroidal neovascularization. Among these, 16 eyes received direct laser photocoagulation of the feeder vessel and did not need any further photodynamic therapy.Conclusion: Previous photodynamic therapy improves the detection of the feeder vessel of the choroidal neovascularization. A sequential combined therapy (photodynamic and feeder vessel treatment) could be considered as an alternative to multiple photodynamic treatments. [ABSTRACT FROM AUTHOR]