Effect of epigallocatechin-gallate on inner retinal function in ocular hypertension and glaucoma: a short-term study by pattern electroretinogram.

BACKGROUND: Epigallocatechin-gallate (EGCG) is a powerful antioxidant with suggested neuroprotective action. The aim of this study was to evaluate the effect of short-term supplementation of EGCG on inner retinal function in ocular hypertension (OHT) and open-angle glaucoma (OAG). METHODS: Eighteen OHT and 18 OAG patients (perimetric mean deviation: >-10 dB) were randomly assigned to assume oral placebo or EGCG over a 3-month period in a randomized, placebo-controlled, double-blind, cross-over design clinical trial (clinicaltrials.gov identifier: NCT00476138). Pattern-evoked electroretinograms (PERGs) to 1.6 cycles/degree square-wave gratings, counterphased at 16 reversals/second, and standard automated perimetry (Humphrey 30-2) were assessed at the study entry (baseline), and after 3 months of placebo or EGCG. RESULTS: After EGCG, PERGs of OAG, but not OHT patients were increased in amplitude, compared either to baseline values (mean amplitude change: 0.06 log microV, p < 0.05) or to PERG amplitude values found in the same patients after placebo administration (mean change: -0.02 log microV, p not significant; difference between EGCG and placebo: 0.08 log microV, p < 0.05). In both OHT and OAG patients, standard automated perimetry did not show significant changes after either EGCG or placebo. In individual OAG patients, the magnitude of PERG amplitude increment after EGCG was inversely related (r = -0.8, p < 0.01) to corresponding baseline amplitudes. CONCLUSIONS: Although this study cannot provide evidence for long-term benefit of EGCG supplementation in OAG, and the observed effect is small, the results suggest that EGCG might favourably influence inner retinal function in eyes with early to moderately advanced glaucomatous damage.

Pattern Electroretinogram Detects Localized Glaucoma Defects.

PURPOSE: We evaluated the clinical ability of pattern electroretinogram (PERG) to detect functional losses in the affected hemifield of open-angle glaucoma patients with localized perimetric defects. METHODS: Hemifield (horizontally-defined) steady-state PERGs (h-PERGs) were recorded in response to 1.7 c/deg alternating gratings from 32 eyes of 29 glaucomatous patients with a perimetric, focal one-hemifield defect, 10 eyes of 10 glaucomatous patients with a diffuse perimetric defect, and 18 eyes of 18 age-matched normal subjects. Standard automated perimetry (SAP) and spectral-domain optical coherence tomography (SD-OCT) for retinal nerve fiber layer (RNFL) thickness also were performed. h-PERG amplitudes and ratios, calculated corresponding hemifield perimetric deviations, as well as hemiretina RNFL thicknesses were analyzed. RESULTS: h-PERG amplitudes, perimetric deviations, and RNFL thicknesses showed losses (P < 0.001) when comparing affected with unaffected hemifields of localized glaucomatous eyes. No differences were found in h-PERG amplitudes between hemifields of normal or diffuse glaucomatous eyes. h-PERG amplitude ratios (affected/unaffected hemifield) in localized glaucoma were lower (P < 0.001) than the ratios from normal or diffuse glaucomatous eyes. The areas under the receiver operating characteristic curves for h-PERG amplitude ratios, comparing localized-defect glaucomatous eyes with normal or diffuse glaucomatous eyes, were 0.93 and 0.91, respectively. CONCLUSIONS: h-PERG assessment showed good diagnostic accuracy to confirm localized glaucomatous defects detected perimetrically. This test may be particularly useful in cognitively impaired patients or young/nonverbal patients unable to provide reliable visual fields. TRANSLATIONAL RELEVANCE: h-PERG provides a sensitive objective measure to confirm focal losses detected with SAP and/or RNFL thickness analysis.

Posterior pole retinal thickness in ocular hypertension and glaucoma: early changes detected by hemispheric asymmetries.

PURPOSE: To evaluate retinal thickness at the posterior pole of the fundus in ocular hypertension (OHT) and open-angle glaucoma (OAG), and to correlate morphometric findings with visual sensitivity as determined by automated perimetry. METHODS: One randomly selected eye from 41 patients with clinical diagnosis of OHT (n = 25) or early to moderate OAG (n = 16) and 16 age-matched normal controls was examined. Retinal thickness was measured by Retinal Thickness Analyzer (RTA), acquiring 5 pre-defined scans covering the central 20 degrees of the fundus. RTA average thickness and thickness profile data, including hemispheric asymmetries calculated as relative (superior/inferior and nasal/temporal) or absolute (vertical and horizontal, ie, independent of which hemisphere was thinner) parameters, were calculated. For each eye, white-on-white Humphrey 30-2 visual field results were analyzed, in addition to standard global indices, by quantifying perimetric sensitivities for regions of the posterior pole corresponding to those sampled by the RTA. RESULTS: On average, central retinal thickness was reduced (P < 0.05) in OAG compared with OHT or normal control eyes. Vertical hemispheric absolute thickness asymmetry was increased (P < or = 0.01) in OAG eyes compared with the other groups. Horizontal hemispheric absolute thickness asymmetry was increased (P < 0.01) in both OHT and OAG eyes, compared with control eyes. At least one of the RTA parameters was altered in 13 of 25 OHT (52%) and 12 of 16 OAG eyes (75%), most frequently involving thickness asymmetries. In OAG, but not OHT eyes, superior/inferior asymmetry was positively (r = 0.69, P < 0.01) correlated with the corresponding asymmetry in perimetric sensitivity. CONCLUSIONS: The RTA can reveal increased hemispheric thickness asymmetries in both OHT and OAG eyes. In OAG eyes thickness asymmetries are associated with corresponding perimetric asymmetries. The findings in OHT eyes suggest that localized anatomic and functional damage to inner retina may not develop in parallel early in the disease process.

Flicker-evoked response measured at the optic disc rim is reduced in ocular hypertension and early glaucoma.

PURPOSE: To determine in patients with ocular hypertension (OHT) or early glaucoma (EOAG) the change in blood flow measured at the neuroretinal rim of the optic disc in response to a 15-Hz diffuse green luminance flicker, a stimulus that activates predominantly the ganglion cell magnocellular pathway. METHODS: Thirteen patients with EOAG, 29 with OHT, and 16 age-matched control subjects, all with excellent fixation, were examined. Blood flow (F(onh)) at the neuroretinal rim of the optic disc was continuously monitored by laser Doppler flowmetry before and during exposure to a 15-Hz, 30 degrees field green luminance flicker. The response of F(onh) to this stimulus (RF(onh)) was expressed as percentage change in F(onh) between baseline and the last 20 seconds of flicker. Two to three temporal sites of the disc were tested, and the highest RF(onh) was considered for further analysis. RF(onh) results in patients were correlated with morphologic (cup-to-disc area ratio, cup shape neuroretinal rim area) and functional (perimetric mean deviation and pattern electroretinogram amplitude) clinical parameters. RESULTS: In the patients with OHT or EOAG, F(onh) and RF(onh) were both reduced compared with their respective values in the control group. Both quantities decreased significantly with neuroretinal rim area when the patients' data were pooled. No significant correlation was found between F(onh) or RF(onh) and the other morphometric and functional parameters. The group-averaged time course of RF(onh) was not significantly different from that in the normal subjects. CONCLUSIONS: Luminance flicker-evoked RF(onh) is abnormally reduced in patients with OHT or EOAG, indicating an impairment of neurally mediated vasoactivity. The data suggest that PERG-derived neural activity and flicker-evoked RF(onh) can be independently altered early in the disease process.

Subfoveal choroidal blood flow and central retinal function in early glaucoma.

PURPOSE: To assess subfoveal choroidal blood flow (ChBF) in patients with early manifest glaucoma (EMG) and to compare blood flow with functional measures of central retinal integrity, standard automated perimetry (SAP) and pattern electroretinogram (PERG). METHODS: Subfoveal ChBF was determined by confocal, real-time laser Doppler flowmetry in 24 patients with EMG [>-6 dB mean deviation (MD), age range: 29-77 years, visual acuity: 20/25-20/20] and 23 age-matched control subjects. All patients had a therapeutically (topical beta-blockers with or without prostaglandin analogues) controlled intraocular pressure (IOP < 20 mmHg). Subfoveal choroidal blood volume (ChBVol), velocity (ChBVel) and ChBF were determined as the average of three 60 second recordings. In all patients and controls, the PERG and SAP (Humphrey 30-2), following standardized protocols, were also recorded. RESULTS: In patients with EMG, reductions in average ChBVel and ChBF were roughly equal, respectively, by 30% and 33.4% (p < 0.01), when compared to control subjects, so that there was no significant difference in ChBVol between the two groups. Pattern electroretinogram amplitudes were reduced by 46% (p < 0.01) in patients compared to controls. No correlation was found between any of the ChBF parameters and PERG amplitude, or Humphrey 30-2 MD and pattern standard deviation. CONCLUSION: The results suggest a significant alteration of both ChBVel and ChBF in EMG, which does not appear to be associated with the severity of central retinal dysfunction. These findings may contribute to a better understanding of the pathophysiology of early glaucomatous damage in EMG and have implications for the treatment of this pathologic condition.

Morpho-functional follow-up of the optic nerve in treated ocular hypertension: disc morphometry and steady-state pattern electroretinogram.

PURPOSE: To examine longitudinally optic disc structure and inner retinal function in treated ocular hypertension (OHT). MATERIALS AND METHODS: A morphometric (Heidelberg Retina Tomograph, HRT) and functional (steady-state pattern electroretinogram, PERG) evaluation of 27 OHT patients treated with topical beta-blockers and/or prostaglandin analogues and prospectively followed over a 24 +/- 6 month period. RESULTS: Compared with baseline, mean final PERG amplitude tended to increase (p < 0.01), while HRT was stable. Individual PERG amplitude increase was large (>or= 100%) in some patients (5/27), and unexplained by clinical parameters at baseline. CONCLUSIONS: In treated OHT, functional responses may improve while disc structure remains stable. The findings suggest that OHT-associated inner retinal dysfunction is at least in part reversible with therapeutic intraocular pressure control.

Structure-function relationship in ocular hypertension and glaucoma: interindividual and interocular analysis by OCT and pattern ERG.

BACKGROUND: Pattern electroretinogram (PERG) and optical coherence tomography (OCT) represent objective probes to investigate respectively the function of retinal ganglion cells and their structure as retinal nerve fiber layer (RNFL) thickness. We examined interindividual (II) correlations of PERG amplitude and RNFL thickness, as well as correlations between interocular (IO) differences in both measures, in ocular hypertension (OHT) and early glaucoma (EG) patients. METHODS: Thirty-one OHT, 34 EG (mean deviation: -1 to -6 dB) and 16 age-matched controls were examined in both eyes. Participants had clear optical media, no or moderate refractive errors and no concomitant ocular or systemic diseases. PERGs were elicited by counterphased (16.28 reversals/second) gratings (1.6 cycles/degree spatial frequency). The Fourier isolated 2nd harmonic PERG amplitude and phase were measured. RNFL thickness was quantified by means of OCT Stratus according to a standard protocol. Average, superior and inferior RNFL thicknesses were considered. RESULTS: Mean PERG amplitude was decreased (p < 0.01) in both OHT and EG patients compared to controls. Mean RNFL thicknesses were reduced (p < 0.01) in EG patients compared to both OHT and controls. In OHT patients, PERG amplitude did not correlate significantly with RNFL thickness in both II and IO analysis. In EG patients, PERG amplitude was positively correlated with RNFL thickness in both II (p < 0.005) and IO (p < 0.001) analysis. The slope of the correlation predicted that PERG losses exceeded systematically RNFL losses when the latter were between 0 and -0.25 log units. CONCLUSIONS: Both II and IO analyses revealed a lack of structure-function relationship in OHT, suggesting that, at this disease stage, PERG losses appear to affect primarily retinal/optic nerve head function. In EG they reflect both dysfunction and RNFL loss.