Diagnosis and classification of macular degenerations: an approach based on retinal function testing.

The results from literature concerning some aspects of retinal function in macular degenerations (MDs) were reviewed in order to evaluate whether (a) specific patterns of retinal dysfunction may be linked to different clinical phenotypes, and (b) distinct functional profiles may help in orienting molecular diagnosis of diseases. Examined clinical phenotypes included: Stargardt disease/fundus flavimaculatus (St/FF), age-related maculopathy (ARM) and macular degeneration (AMD), pattern dystrophies (PD), Best vitelliform dystrophy (BVD), Sorsby's fundus dystrophy (SFD), autosomal cone-rod dystrophies (CRD). The following functional tests were evaluated: (1) electroretinogram (ERG) (scotopic and photopic according to ISCEV standards, rod and cone photoresponses, rod and cone b-wave intensity-response function, focal ERGs); (2) dark adaptometry (pre-bleach sensitivity and post-bleach recovery kinetics); (3) fundus reflectometry (pigment density and regeneration kinetics). Specific patterns of retinal dysfunction were identified for St/FF, ARM/AMD, SFD and BVD, whereas partially overlapping profiles were found for PD and CRD. Specific functional patterns were associated with different peripherin/RDS gene mutations, as well as with CRX mutations. Combined analysis of different retinal function tests may help to identify different phenotypes of MD, and to orient molecular diagnosis for selected genotypes.

Correlation of optic nerve head tomography with visual field sensitivity in papilledema.

PURPOSE: To quantify the relationship between optic nerve head tomography and perimetric sensitivity in patients with papilledema. METHODS: Eight patients with variable degrees of recently diagnosed papilledema associated with idiopathic intracranial hypertension (IIH) were evaluated with confocal scanning laser ophthalmoscopy (CSLO) and automated perimetry. Patients were followed up with serial measurements over a period of 5 to 30 months (mean +/- SD, 17.1 +/- 9), while under medical treatment (acetazolamide). The tomographic parameters, volume above reference (VAR), volume above surface (VAS), effective mean height (EMH), and maximum height in contour (MxHC), were obtained by tomography, either globally or from predefined disc sectors. The perimetric indices, mean deviation (MD) and pattern SD (PSD), were evaluated. The results from patients' right eyes and the individual intereye differences in both tomographic and perimetric parameters, were statistically evaluated by nonparametric correlational (Spearman) and repeated measures (Wilcoxon) analyses. RESULTS: At baseline, all tomographic parameters were negatively correlated with MD in global (r = -0.8) and sectorial (r = -0.6) evaluations. The interocular differences in overall tomographic parameters were correlated with corresponding differences in perimetric MD (r = -0.8) and PSD (r = 0.6). During the follow-up period, volumetric disc parameters decreased (P < 0.02), whereas perimetric MD increased (P = 0.02) at comparable times. CONCLUSIONS: In patients with recently diagnosed papilledema, optic nerve head tomographic abnormalities are quantitatively correlated with visual field sensitivity losses. Therapeutic improvement of volumetric parameters may be paralleled by recovery in perimetric sensitivity. The data support the possible use of both techniques in combination to monitor the amount of papilledema and the effectiveness of treatments designed to reduce intracranial hypertension.

Ultrasonographic evaluation of optic disc swelling: comparison with CSLO in idiopathic intracranial hypertension.

PURPOSE: To determine the accuracy and reproducibility of ultrasonographic (US) readings of optic disc elevations in patients with papilledema compared with confocal scanning laser ophthalmoscope (CSLO) measurements. METHODS: One randomly selected eye of 22 patients with idiopathic intracranial hypertension (IIH) and a variable degree of optic disc swelling underwent five and three repeated measurements of disc height using high-resolution ultrasonography (Biovision unit; Quantel Medical, Clermont-Ferrand, France) and CSLO (Heidelberg Retina Tomograph [HRT]; Heidelberg Engineering, Heidelberg, Germany), respectively. The same procedure was assessed in 14 subjects with variable degrees of physiologic optic disc cupping. US and HRT measurements from each group were individually compared with each other to estimate the accuracy of US readings in both disc conditions in comparison with HRT data. RESULTS: Ultrasonographic readings were positively correlated with HRT measurements in both swollen (r = 0.62, P: = 0.002) and excavated disc (r = 0.84, P: < 0.0002). The 95% limits of agreement between the instruments were 0.24 +/- 0.59 mm (mean +/- 2 SD) and 0. 05 +/- 0.3 mm for swelling and cupping measurements, respectively. The coefficient of variation was 7.63% and 1.8% for swelling and 7. 93% and 5.91% for cupping, with US and HRT, respectively. CONCLUSIONS: The results indicate that US and CSLO readings are correlated i: both disc swelling and cupping conditions, but to a different extent because of a significant discrepancy in papilledema. US assessment can be considered highly reproducible. Combined US and HRT optic disc analysis may be recommended in papilledema evaluation as long as a better correlation can be demonstrated in further studies.

Photopic negative response of the human ERG: losses associated with glaucomatous damage.

PURPOSE: To evaluate in glaucomatous eyes the photopic electroretinogram (ERG) negative response (PhNR), a component that follows the b-wave peak and is thought to be correlated with inner retinal activity. METHODS: Eleven patients with open-angle glaucoma (OAG) and moderate field loss (Humphrey 30-2 [Humphrey Instruments, San Leandro, CA] mean deviation < or = -6 dB), eight with ocular hypertension (OHT), and eight age-matched normal subjects were tested. Optic discs of patients and control subjects were evaluated by confocal scanning laser ophthalmoscopy. ERGs were recorded to long-duration stimuli (250 msec) of photopic luminance (78 candelas [cd] /m2), presented in the macular region (12 degrees x 12 degrees field size) on a steady, adapting background. Amplitudes of the a-wave and b-wave and the PhNR were measured. Pattern reversal ERGs to 30-minute checkerboards were also recorded from patients and control subjects. RESULTS: Compared with control subjects, patients with OAG showed reduced PhNR (average reduction: 62%, P < 0.01), but normal a- and b-wave amplitudes. In patients with OHT, PhNR and a- and b-wave amplitudes did not differ from control values. In individual patients with OAG, PhNR amplitudes were correlated positively with pattern ERG amplitudes (r = 0.80; P < 0.01) and central (12 degrees) perimetric mean deviations (r = 0.68; P < 0.05) and negatively with cup-to-disc area ratios (r = -0.79; P < 0.01) and cup shape measures (r = -0.78; P < 0.01). CONCLUSIONS: Similar to that found in monkeys with experimentally induced glaucoma, the PhNR is selectively altered in human glaucoma. The correlation between PhNR losses and clinical parameter abnormalities suggests that this component depends on inner retina integrity and may be of clinical value for detecting glaucomatous damage.

Retinal sensitivity to flicker modulation: reduced by early age-related maculopathy.

PURPOSE: To evaluate retinal, cone-mediated flicker sensitivity (CFS) in age-related maculopathy (ARM) by quantifying response gain and threshold of the focal electroretinogram (FERG) to flicker modulation. METHODS: Nineteen patients with ARM (visual acuity > or =20/30) and 11 age-matched control subjects were examined. Twelve patients had less than 20 soft drusen in the macular region and no hyper-/hypopigmentation (early lesion), whereas seven had more than 20 soft drusen and/or focal hyper-/hypopigmentation (advanced lesion). Macular (18 degree ) FERGs were elicited by a sinusoidally flickering (41 Hz) uniform field (on a light-adapting background) whose modulation depth was varied between 16.5% and 94%. Amplitude and phase of the response's fundamental harmonic were measured. RESULTS: In both control subjects and patients with ARM, log FERG amplitude increased with log stimulus modulation depth with a straight line (power law) relation. However, the slope (or gain) of the function was, on average, steeper in control subjects than in patients with either early or advanced lesions. Mean FERG threshold, estimated from the value of the log modulation depth that yielded a criterion response, did not differ between control subjects and patients with early lesions but was increased (0.35 log units) compared with control subjects in those with advanced lesions. In both patient groups, but not in control subjects, mean FERG phase tended to delay with decreasing stimulus modulation depth. CONCLUSIONS: Retinal CFS losses can be detected in ARM by evaluating the FERG as a function of flicker modulation depth. Reduced response gain and phase delays, with normal thresholds, are associated with early lesions. Increased response thresholds, in addition to gain and phase abnormalities, may reflect more advanced lesions. Evaluating CFS by FERG may directly document different stages of macular dysfunction in ARM.

The role of ocular oscillations upon visually dependent postural stabilization in patients affected by congenital nystagmus.

Visually dependent postural stabilization decreases as a consequence of a long-standing reduction of visual cues in patients affected by congenital nystagmus. The aim of the present study was to verify whether the changes in postural control in this group of patients are due to ocular oscillations or to reduced visual acuity. Therefore, postural control was evaluated when the nystagmus was blocked by the blocking position or by prisms and compared with the postural score observed in a group of normal controls whose visual acuity had been artificially reduced to the same level as that of the patients using Bangerter's filters. The results show a statistically significant improvement of visually dependent postural stabilization when ocular oscillations are inhibited either by the gaze blocking position or by prisms. They also show that postural control in normal subjects with Bangerter's filters is reduced, but is still significantly better than that observed when ocular oscillations are inhibited in patients affected by congenital nystagmus. Our data strongly support the role of ocular oscillations in visually dependent postural control, since postural impairment recovered under any condition in which ocular oscillations were abolished, despite differences in visual acuity. Our data also show that reduced visual acuity decreases visually dependent postural control to a lesser degree than ocular oscillations. This could be due to the fact that ocular oscillations are a disturbing input, usually inhibited centrally, in order to avoid oscillopsia. This mechanism is probably responsible for the reduced role of visual cues in the postural control in this group of patients. The reduction of visual acuity, by comparison, merely causes a decrease in visual cues, depending on the degree of visual loss. It can be concluded that the impaired postural control in patients affected by congenital nystagmus is mainly due to ocular oscillations, with reduced visual acuity creating a secondary effect.

The fundamental and second harmonic of the photopic flicker electroretinogram: temporal frequency-dependent abnormalities in retinitis pigmentosa.

OBJECTIVES: The flicker electroretinogram (FERG) consists mainly of a linear (fundamental, 1F) and a non linear (second harmonic, 2F) component. Previous results indicate that 2F originates more proximally in the retina than 1F, and that retinitis pigmentosa (RP) may affect 2F to a greater extent than 1F. The aim of this study was to evaluate FERG 1F and 2F abnormalities in RP as a function of the stimulus temporal frequency (TF). METHODS: Twelve patients with typical RP and 10 age-matched controls were examined. FERGs were recorded in response to uniform fields (18 degrees) presented in the macula on a light-adapting background. Stimuli were flickered sinusoidally at different, closely spaced TFs between 3.7 and 52 Hz. Amplitudes and phases of the Fourier analysed 1F and 2F components were measured. Components' apparent latencies were estimated from the rate at which phase lagged with TF. RESULTS: When compared to controls, mean 1F amplitudes of patients were reduced at both low (3.7-12.6 Hz) and high (14-52 Hz) TFs, with greatest losses (0.5 log units) around the peaks (3.7 and 41 Hz) of the normal TF function. Mean 2F amplitudes were reduced mainly at low TFs, with greatest losses (0.5 log units) at 5-8 Hz. On average, the shape of the 2F, but not 1F amplitude versus TF function, differed between patients and controls, showing a selective attenuation at low TFs. Mean 1F apparent latencies were delayed at both low and high TFs, with greater delays at low (85 ms) than at high (33 ms) TFs. Mean 2F apparent latencies were delayed only at low TFs (58 ms). CONCLUSIONS: In RP, 1F and 2F phase delays as well as 2F amplitude losses are dependent on TF, suggesting that FERG generators' subpopulations in both distal and proximal retina are differentially affected. Analysis of the FERG TF response is potentially useful to characterize cone system dysfunction in different genetic subtypes of RP.

Correlation of pattern electroretinogram with optic disc cup shape in ocular hypertension.

PURPOSE: To evaluate the correlation of pattern electroretinogram (PERG), an index of inner retinal function, with confocal scanning laser (CSLO) optic disc structural parameters in ocular hypertension (OHT). METHODS: Thirty-four patients with OHT, normal white-on-white (Humphrey 30-2) perimetry, and normal clinical optic discs were examined with PERG and CSLO disc analysis. Two groups of normal subjects (n = 38 and 18, for PERG and CSLO, respectively) and a group of 12 patients with early open-angle glaucoma (EOAG) were also tested. Pattern electroretinogram amplitudes were measured in response to sinusoidal gratings of variable spatial frequency (0.58-5.8 cycles/degree), modulated in counter-phase at 7.5 Hz. Morphometric optic disc parameters were obtained by the Heidelberg Retina Tomograph (HRT), either globally or from predefined disc sectors. In addition to standard parameters, the cup shape measure, an index of depth variation and steepness of the cup walls, was determined. RESULTS: In individual OHT patients, PERG amplitudes at 2.6 cycles/degree were negatively correlated with cup shape measures (r = -0.43, P < 0.01) obtained from analysis of the inferotemporal (IT) sector. No significant correlations were found for the other parameters. On average, the cup shape measures derived from IT sector or global analysis were significantly (P < 0.01) worse, and closer to the measures of EOAG patients, in OHT patients with abnormal PERG compared with those with normal PERGs. The cup shape measure displayed a low sensitivity (20%) and a high specificity (100%) in predicting PERG abnormalities in individual OHT patients. CONCLUSIONS: The results indicate that in OHT there is a significant although weak correlation between PERG amplitude and the shape of the optic disc cup, suggesting a parallel involvement of both function and morphology. Combined PERG and optic disc cup structural analysis is of potential diagnostic value to detect early damage to optic nerve head in individual OHT patients.

A new device for ocular surgical training on enucleated eyes.

OBJECTIVE: To develop a reliable inexpensive device for teaching ocular surgical procedures and practicing experimental techniques on enucleated eyes. DESIGN: Teaching device trial. PARTICIPANTS: Thirty enucleated porcine eyes. METHODS: A Plexiglas ocular bulb holder was secured with its base support to a polyvinylchloride pillar on a modified polystyrene trial head. MAIN OUTCOME MEASURE: The convenience and reproducibility of both laser and surgical ocular techniques performed with this new device were evaluated. RESULTS: This model allows curvilinear capsulorrhexis and phacoemulsification of porcine lenses through a corneal tunnel incision and insertion of a soft foldable acrylic intraocular lens into the capsular bag. Argon and neodymium:YAG laser iridotomy and retinal argon laser photocoagulation can also be performed with this model. CONCLUSIONS: This inexpensive device is useful for teaching both surgical and laser ocular procedures.

Conservative treatment of adnexal, epibulbar and intraocular neoplasms by means of electron microbeams: a preliminary study.

At present, episcleral plaque brachytherapy and charged particle or photon irradiation are the most commonly employed methods in ocular and adnexal conservative treatments. In the near future, a different therapeutic approach to these malignancies could be represented by a new device based on electron beam emission. The equipment used consists of an electron accelerator originally developed for intraoperative radiotherapy, modified to fit ocular pathologies. Adequate collimators and an enhanced mechanical accuracy are required for this special practice. An operative planning for epibulbar, adnexal and intraocular tumors is described, discussing its rationale for possible applications. Experimental tests using phantoms and Gafchromic(R) films are in progress. As all conservative treatments, the main gaol of this activity is the maintenance of a good visual function.

Pattern electroretinogram and optic nerve topography in ocular hypertension.

It is known that changes in pattern electroretinogram (PERG) and optic disk morphology may both precede the onset of visual field damage in glaucomatous disease. However, the relationship between PERG and optic disk morphometry in ocular hypertension (OHT) has not yet been evaluated in detail. This study of PERG amplitude in a group of OHT patients indicates its significant correlation with various optic disk morphometric parameters, in particular, those of optic disk sectors considered at risk for early glaucomatous damage. Analysis of individual data points to the possibility that, while functional abnormalities may often precede optic disk morphologic changes, in a much lower number of cases it seems to be the other way around.

VDU work: longitudinal survey on refractive defects.

A longitudinal survey in two different phases with an interval of 4 years (including more than 23,000 employees) has been carried out to study whether the time spent using VDU (daily hours and years of work) can change the refractive state. With reference to the whole sample including all refractions, there was no significant difference in the refractive state in employees who spent varying daily hours or years working at VDU. Furthermore, there were no significant changes in the refractive states of emmetropic, hypermetropic and myopic subjects, with regard to the time spent working at VDU. The data have shown that a high exposure to VDU work (more than 6 h per day or more than 6 years spent working at a VDU) is not responsible for inducing or worsening refractive error.

Trends regarding myopia in video terminal operators.

A longitudinal study with a 4-year follow-up was carried out on 6101 employees of the Italian Telecommunications Company (Telecom Italia) to study the role of work at Video Display Units (VDU) for the evolution of different types of myopia (mild, intermediate and pathologic). The refractive modifications of myopic VDU operators were further studied with regard to differences in time of use of VDU (daily hours and years spent working at a VDU). No statistically significant difference was found for refractive modifications, neither with regard to the type of myopia, nor to the daily hours and years spent working at a VDU. The results have indicated that the use of VDU is not responsible for a worsening of myopia.

Psychology of computer use: XXXVI. Visual discomfort and different types of work at videodisplay terminals.

The relationship between visual discomfort (or asthenopia) and different types of work using display units for 10,626 videodisplay terminal operators of the Italian Telecommunication Company was studied. Visual discomfort was evaluated as related to data entry, data checking, word processing, dialogue, enquiry, and various services. Chi-squared indicated that visual discomfort was not significantly related to any particular type of work for subjects with similar amounts of weekly time using videodisplay units. These findings are consistent with earlier results indicating that the main factor determining visual fatigue in VDT operators is the amount of time spent on the display units.

Protective filters in the prevention of asthenopia at a video display terminal.

In this work 25,064 employees were studied with the aim of investigating whether the video display terminal (VDT) equipped with filters reduces the incidence of asthenopia with reference to weekly time spent at a VDT and duration of work at a VDT. Analysis showed that the filters themselves do not reduce the occurrence of asthenopia consequent to various factors (refractive defects, time spent at a VDT, and monitors' characteristics).