Angelo Maria Minnella

Nonselective Loss of Contrast Sensitivity in Visual System Testing in Early Type I Diabetes

Objective Psychophysical methods in patients with diabetes mellitus reveal deficits of central or foveal vision. Our aim was to evaluate the contrast-sensitivity thresholds in 24 insulin-dependent (type I) diabetic patients with a short disease duration and without retinopathy, taking into account metabolic control. Research Design and Methods The control group consisted of age-matched nondiabetic subjects. None had visual or systemic symptoms. Contrast sensitivity measured at eight different spatial frequencies to sinusoidal bar patterns of 0.6–12.2 cycles/deg can detect functional defects in the spatially sensitive retinal ganglion cells or in higher visual pathways. We performed two different temporal types of contrast-sensitivity testing, dynamic (8 Hz) and static (0 Hz). Results Significant losses with dynamic contrast-sensitivity test at all but the highest spatial frequencies (i.e., 12.2 cycles/deg) were shown, whereas there was significant attenuation of contrast sensitivity at five spatial frequencies (1.0, 1.4, 2.2, 7.1, and 9.6 cycles/deg) in the static mode. Grating losses (<2SD of control means) of contrast sensitivity were found in 33.3% (dynamic) and in 72.9% (static) of eyes of diabetic patients. HbA1c values were positively correlated at variable spatial frequencies (1.0, 1.4, and 2.2 cycles/deg for dynamic test and 0.6, 1.0, 1.4, 2.2, 4.8, and 7.1 cycles/deg for static test). Conclusions Our results suggest an early, generally nonselective neuronal damage of visual pathways that occurs before the onset of clinically detectable retinopathy. The visual deficit may be related directly to the effects of diabetes; repetitive minor hypoglycemic insults may contribute more than a marked hyperglycemic condition to the mechanisms underlying physiological changes along the optic nerve.

Intravitreal bevacizumab (Avastin®) in proliferative diabetic retinopathy

Purpose:  To evaluate the efficacy and safety of intravitreal bevacizumab in proliferative diabetic retinopathy (PDR) patients.

Steady-state pattern electroretinogram in insulin-dependent diabetics with no or minimal retinopathy

Steady-state pattern electroretinogram (PERG) in response to sinusoidal gratings (1.7 c/deg spatial frequency; 9 × 9 deg field size) temporally modulated (sinusoidally) at 8 Hz were recorded in 40 insulin-dependent diabetics and 28 age-matched normal subjects. Visual acuity was ⩾ 20/20 in all 40 patients; 31 (62 eyes) showed no sign of retinopathy and nine (18 eyes) showed a few microaneurysms on fluorescein angiography. Insulin-dependent diabetics showed a significant reduction in the PERG mean amplitude as compared with age-matched control subjects (one-way analysis of variance: p < 0.0001). Significant differences were observed between normals and diabetics without retinopathy (Scheffé test: p < 0.0001), normals and diabetics with early retinopathy (Scheffé test: p < 0.0001), no retinopathy and early retinopathy patients (Scheffé test: p < 0.05). In diabetics without retinopathy multi-factorial analysis of variance revealed a significant effect of age of onset of the disease (p < 0.01) and an interaction effect between age of onset and duration (p < 0.001) on PERG amplitude. These results suggest a possible use of the steady-state PERG to detect early macular dysfunction in insulin-dependent diabetics.

A Longitudinal Follow-Up Study of Saffron Supplementation in Early Age-Related Macular Degeneration: Sustained Benefits to Central Retinal Function

Objectives. In a previous randomized clinical trial (Falsini et al. (2010)), it was shown that short-term Saffron supplementation improves retinal flicker sensitivity in early age-related macular degeneration (AMD). The aim of this study was to evaluate whether the observed functional benefits from Saffron supplementation may extend over a longer follow-up duration. Design. Longitudinal, interventional open-label study. Setting. Outpatient ophthalmology setting. Participants. Twenty-nine early AMD patients (age range: 55–85 years) with a baseline visual acuity >0.3. Intervention. Saffron oral supplementation (20 mg/day) over an average period of treatment of 14 (±2) months. Measurements. Clinical examination and focal-electroretinogram-(fERG-) derived macular (18°) flicker sensitivity estimate (Falsini et al. (2010)) every three months over a followup of 14 (±2) months. Retinal sensitivity, the reciprocal value of the estimated fERG amplitude threshold, was the main outcome measure. Results. After three months of supplementation, mean fERG sensitivity improved by 0.3 log units compared to baseline values (P < 0.01), and mean visual acuity improved by two Snellen lines compared to baseline values (0.75 to 0.9, P < 0.01). These changes remained stable over the follow-up period. Conclusion. These results indicate that in early AMD Saffron supplementation induces macular function improvements from baseline that are extended over a long-term followup.

Differential vulnerability of retinal layers to early age-related macular degeneration: Evidence by SD-OCT segmentation analysis

PURPOSE We evaluated layer-by-layer retinal thickness in spectral-domain optical coherence tomography (SD-OCT), determined by automated segmentation analysis (ASA) software in healthy and early age-related maculopathy (ARM) eyes. METHODS There were 57 eyes (specifically, 19 healthy eyes under 60 years old, 19 healthy eyes over 60, and 19 ARM eyes) recruited into this cross-sectional study. The mean ages were 36.78 (SD, ±13.82), 69.89 (SD, ±6.14), and 66.10 (SD, ±8.67) years, respectively, in the three study groups. The SD-OCT scans were transferred into a dedicated software program that performed automated segmentation of different retinal layers. RESULTS Automated layer segmentation showed clear boundaries between the following layers: retinal nerve fiber layer (RNFL), ganglion cell layer plus inner plexiform layer (GCL+IPL), inner nuclear layer plus outer plexiform layer (INL+OPL), outer nuclear layer (ONL), and RPE complex. The thickness of the RNFL, ONL, and RPE layers did not show a statistically significant change across the three groups by ANOVA (P = 0.10, P = 0.09, P = 0.15, respectively). The thickness of GCL+IPL and INL+OPL was significantly different across the groups (P < 0.01), being reduced in the ARM eyes compared to healthy eyes, under and over 60 years old. CONCLUSIONS The early morphologic involvement of the GCL+IPL and INL+OPL layers in ARM eyes, as revealed by the ASA, could be related to early anatomic changes described in the inner retina of ARM eyes. This finding may represent a morphologic correlation to the deficits in postreceptoral retinal function in ARM eyes.

Macular functional changes evaluated with MP-1 microperimetry after intravitreal bevacizumab for subfoveal myopic choroidal neovascularization: one-year results.

Purpose: The purpose of this study was to evaluate 1-year functional and structural effects of intravitreal bevacizumab for subfoveal choroidal neovascularization secondary to pathologic myopia (myopic choroidal neovascularization). Methods: Fifteen eyes with myopic choroidal neovascularization participated in this prospective interventional, noncomparative case series. All patients were treated with one intravitreal injection of 1.25 mg bevacizumab. Retreatments were performed in case of persistent or recurrent leakage on fluorescein angiography and/or intraretinal fluid on optical coherence tomography. Evaluation of best-corrected visual acuity using Early Treatment of Diabetic Retinopathy Study criteria, MP-1 microperimetry, optical coherence tomography, and fluorescein angiography were performed before treatment and 1 month, 3 months, 6 months, and 1 year after treatment. Results: After a follow-up of 12 months, best-corrected visual acuity improved on average of 0.23 logarithm of the minimum angle of resolution. Mean macular sensitivity within the central 8° increased on average of 2.62 dB at 12-month postinjection. The mean number of measurement points within the central absolute scotoma reduced significantly from 12.47 before treatment to 6.27 at 1-year follow-up. An improvement of fixation stability from baseline was observed in 9 patients (60%). No treatment adverse events were evidenced. Conclusion: Improvement of macular sensitivity and fixation stability 1 year after intravitreal bevacizumab for myopic choroidal neovascularization suggest a stable and progressive macular function recovery. The mean treatment session was 1.53, with 53.3% of patients needing only a single intravitreal bevacizumab injection, supporting a potential long-lasting efficacy of intravitreal bevacizumab treatment.

Functional effect of Saffron supplementation and risk genotypes in early age-related macular degeneration: a preliminary report.

BackgroundTo determine whether the functional effects of oral supplementation with Saffron, a natural compound that proved to be neuroprotective in early age-related macular degeneration, are influenced by complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) risk genotypes.MethodsThirty-three early AMD patients, screened for CFH (rs1061170) and ARMS2 (rs10490924) polymorphisms and receiving Saffron oral supplementation (20 mg/day) over an average period of treatment of 11 months (range, 6–12), were longitudinally evaluated by clinical examination and focal electroretinogram (fERG)-derived macular (18°) flicker sensitivity estimate. fERG amplitude and macular sensitivity, the reciprocal value of the estimated fERG amplitude threshold, were the main outcome measures.ResultsAfter three months of supplementation, mean fERG amplitude and fERG sensitivity improved significantly when compared to baseline values (p < 0.01). These changes were stable throughout the follow-up period. No significant differences in clinical and fERG improvements were observed across different CFH or ARMS2 genotypes.ConclusionsThe present results indicate that the functional effect of Saffron supplementation in individual AMD patients is not related to the major risk genotypes of disease.

MACULAR FLICKER ELECTRORETINOGRAMS IN BEST VITELLIFORM DYSTROPHY

PURPOSE The aim of this study was to evaluate the function of the neurosensory retina in Best vitelliform macular dystrophy (BMD) by recording the focal electroretinogram (ERG) fundamental and 2nd harmonic components, which are known to be dominated by receptoral and postreceptoral activity, respectively. METHODS FERGs were recorded in response to a uniform field (9 x 9 deg) flickered sinusoidally at either 8 Hz or 32 Hz (peak frequencies for the 2nd and fundamental harmonic, respectively). The fundamental component of the response to the 32-Hz stimulus and the 2nd harmonic of the response to the 8-Hz stimulus were measured in their amplitudes and phases. The fundamental-2nd harmonic amplitude ratio was taken as an index of the relative changes in the FERG components. Eleven patients with BMD and vitelliform stage macular lesions were evaluated. Results were compared with those obtained from 13 patients with Type 2 Stargardt macular dystrophy (STD) according to the Noble and Carr Classification, and 29 normal control subjects. Four BMD and four STD patients were also followed electrophysiologically over a 48 month period. RESULTS Compared to controls, BMD patients showed losses of both FERG fundamental and 2nd harmonic amplitudes, and an increase in the fundamental and increase in the fundamental-2nd harmonic ratio. STD patients also showed losses of both fundamental and 2nd harmonic, but the fundamental-2nd harmonic ratio was normal. In BMD patients, but not in those with STD, the fundamental amplitude tended to decrease over the follow-up period. CONCLUSIONS The results indicate that BMD involves neurosensory abnormalities early in the disease process. The increased fundamental-2nd harmonic ratio suggests that a postreceptoral dysfunction may be present in addition to that of photoreceptors. This differs from STD, where losses appear to affect primarily the receptoral retina. Receptoral losses in BMD may progress throughout the medium-term follow up.

Regional cone-mediated dysfunction in age-related maculopathy evaluated by focal electroretinograms: relationship with retinal morphology and perimetric sensitivity.

Purpose: To assess regional cone-mediated function in age-related maculopathy (ARM) by focal electroretinograms (FERGs), and to compare FERGs with morphologic changes and perimetric sensitivity at corresponding locations. Methods: Twenty-six ARM patients and 12 age-matched controls were evaluated. FERGs were elicited by either a central (0–2.25°, C) or a paracentral annular (2.25–9°, PC) flickering (41 Hz) field, presented on a light-adapting background. Morphological changes (soft drusen and/or retinal pigment epithelium defects) at matched locations were assessed by fundus photography and fluorescein angiography. Perimetric sensitivity was measured by Octopus 10° program (tM2). Results: When compared to controls, mean C and PC FERG amplitudes of patients were reduced (p < 0.01), and the mean PC FERG phase was delayed (p < 0.01). Both FERG delays and morphologic lesions tended to involve to a greater extent the PC compared to the C region. In the C region, perimetric losses were correlated with the extent of morphologic lesions (p < 0.05). In the PC region, perimetric losses were correlated with FERG amplitudes (p < 0.05). Conclusions: In ARM, FERG losses are eccentricity-dependent, not quantitatively linked to retinal morphology, and correlated with perimetric losses, suggesting a heterogeneous dysfunction with loss of both C and PC perimetric sensitivities.

Macular electroretinograms to flicker and pattern stimulation in lamellar macular holes

Steady-state macular (9° × 9°) electroretinograms in response to either sinusoidal flicker (focal electroretinogram) or counterphased sinusoidal gratings (pattern electroretinogram) were recorded in 14 patients with inner lamellar macular holes, in 4 patients with full-thickness macular holes and in 14 age-matched controls. Fourier analysis of focal and pattern electroretinograms yielded three main components: a first and a second harmonic to flicker, and a second harmonic to pattern. Recent evidence indicates that the first harmonic to flicker is of receptoral origin, whereas the flicker and pattern second harmonics represent, at least in part, the activity of different generators in the inner retina. When compared to controls, patients with inner lamellar holes showed significant amplitude reduction and phase delay for both flicker and pattern second harmonics, but not for the flicker first harmonic. Patients with full-thickness holes showed significant amplitude reduction also for the flicker first harmonic. These results indicate a prevalent functional involvement of the inner retina in lamellar macular holes, which can be clinically detected by evaluating focal and pattern electroretinogram second harmonics.