Peroxisomal and mitochondrial defects in the cerebro-hepato-renal syndrome.

The cerebro-hepato-renal syndrome is a rare familial malady with cerebral, renal, and skeletal abnormalities, severe hypotonia, cirrhosis, iron and lipid storage, and death within 6 months. Correlated electron microscopic, histochemical, and biochemical studies demonstrate defects in two oxidative organelles. Peroxisomes cannot be found in hepatocytes and renal proximal tubules. In hepatocytes and cortical astrocytes, mitochondria are distorted in their appearance and glycogen stores are increased. Oxygen consumnption of brain and liver mitochondrial preparations with succinate and with substrates reducing nicotinamide adenine dinucleotide is markedly diminished, but the consumption is normal with ascorbate and tetramethylphenylenediamine, which suggests a defect in electron transport prior to the cytochromes. Histochemical studies of mitochondrial oxidation point to a defect between the succinate dehydrogenase flavoprotein and coenzyme Q, possibly in the region of nonheme iron protein.

Identification of a gene that causes primary open angle glaucoma.

Glaucoma is a major cause of blindness and is characterized by progressive degeneration of the optic nerve and is usually associated with elevated intraocular pressure. Analyses of sequence tagged site (STS) content and haplotype sharing between families affected with chromosome 1q-linked open angle glaucoma (GLC1A) were used to prioritize candidate genes for mutation screening. A gene encoding a trabecular meshwork protein (TIGR) mapped to the narrowest disease interval by STS content and radiation hybrid mapping. Thirteen glaucoma patients were found to have one of three mutations in this gene (3.9 percent of the population studied). One of these mutations was also found in a control individual (0.2 percent). Identification of these mutations will aid in early diagnosis, which is essential for optimal application of existing therapies.

Urrets-Zavalia syndrome as a complication of argon laser peripheral iridoplasty.

OBJECTIVE: To report on 8 patients who developed prolonged mydriasis after argon laser peripheral iridoplasty (ALPI). DESIGN: Retrospective case series. METHODS: A review of the charts of 8 patients with persistent occludable angles after laser iridotomy who developed mydriasis after undergoing ALPI. RESULTS: 12 eyes of 8 patients (mean age 50.2, standard deviation 6.9, range 40-61 years) developed persistent dilatation. 7 of 8 patients had plateau iris syndrome. Only one patient had a decrease in visual acuity. Intraocular pressure increased only in 1 eye and remained stable or decreased in the others. Of the 8 patients, 7 had blurred vision, 2 had photophobia, 4 had glare and 1 had discomfort. The pupillary response to pilocarpine instillation was minimal or absent. Mydriasis eventually resolved in all eyes without treatment. CONCLUSION: ALPI can be complicated by mydriasis unresponsive to pilocarpine. Mydriasis and accompanying symptoms resolved spontaneously within 1 year in most patients.

Axial length and optic disc size in normal eyes.

AIM: To investigate the relationship between optic disc area and axial length in normal eyes of white and black people. METHODS: Consecutive eligible normal subjects were enrolled. Ocular biometry was obtained using A-scan ultrasonography, and reliable images of the optic disc were obtained using a confocal scanning laser ophthalmoscope. The relationship between optic disc area and axial length was assessed using univariate and multivariate models. RESULTS: 281 eyes of 281 subjects were enrolled. Black subjects (n = 157) had significantly larger discs (mean (SD) disc area, 2.12 (0.5) mm(2)) than white subjects (n = 124; 1.97 (0.6) mm(2); t test, p = 0.02). Optic disc area increased with axial length (Pearson's correlation coefficient, r = 0.13, p<0.035) for the entire study population. Multivariate regression models including race, disc area and axial length showed that a significant but weak linear relationship exists between axial length and disc area (partial correlation coefficient 0.14; p<0.024), and with race and disc area (partial correlation coefficient 0.19; p<0.017) when adjusted for the effects of other terms in the model. CONCLUSION: Increased disc area is associated with longer axial length measurements and African ancestry. This may have implications for pathophysiology and risk assessment of glaucoma.

Retinal nerve fibre thickness measured with optical coherence tomography accurately detects confirmed glaucomatous damage.

AIM: To assess the accuracy of optical coherence tomography (OCT) in detecting damage to a hemifield, patients with hemifield defects confirmed on both static automated perimetry (SAP) and multifocal visual evoked potentials (mfVEP) were studied. METHODS: Eyes of 40 patients with concomitant SAP and mfVEP glaucomatous loss and 25 controls underwent OCT retinal nerve fibre layer (RNFL), mfVEP and 24-2 SAP tests. For the mfVEP and 24-2 SAP, a hemifield was defined as abnormal based upon cluster criteria. On OCT, a hemifield was considered abnormal if one of the five clock hour sectors (3 and 9 o'clock excluded) was at <1% (red) or two were at <5% (yellow). RESULTS: Seventy seven (43%) of the hemifields were abnormal on both mfVEP and SAP tests. The OCT was abnormal for 73 (95%) of these. Only 1 (1%) of the 100 hemifields of the controls was abnormal on OCT. Sensitivity/specificity (one eye per person) was 95/98%. CONCLUSIONS: The OCT RNFL test accurately detects abnormal hemifields confirmed on both subjective and objective functional tests. Identifying abnormal hemifields with a criterion of 1 red (1%) or 2 yellow (5%) clock hours may prove useful in clinical practice.

Nailfold capillary morphology in exfoliation syndrome.

PurposeThe purpose of the study was to investigate nailfold microvascular morphology in exfoliation syndrome with or without glaucoma (XFS/XFG) compared with primary open-angle glaucoma (POAG) and control subjects using nailfold capillary videomicroscopy.Patients and methodsWe used a JH-1004 capillaroscope to perform nailfold capillary videomicroscopy on the fourth and fifth digit of the non-dominant hand. We enrolled 56 XFS/XFG patients, 87 POAG patients, and 75 control subjects. Masked observers graded the videos for hemorrhages, avascular zones ≥200 microns (µm), and degree of microvascular tortuosity on a four-point subjective scale. Multivariable odds ratios, 95% confidence intervals and P-for trends for assessing the relation between morphological changes and POAG or XFS/XFG were obtained from logistic regression analyses. We also assessed this relation with XFS/XFG compared with POAG in multivariable models.ResultsAfter adjusting for multiple covariates, nailfold hemorrhages, avascular zones ≥200 µm, and higher degree of vascular tortuosity were more common in XFS/XFG vs controls (P-for trend ≤0.0001) and in POAG vs controls (P-for trend ≤0.01). For each 100 capillaries, the number of hemorrhages was similar (P-for trend=0.91) between XFS/XFG and POAG patients; however, there were more avascular zones per 100 capillaries with borderline significance (P-for trend=0.04) in the XFS/XFG group. XFS/XFG patients had more tortuosity than POAG patients; specifically, having a tortuosity score ≥1.5 was associated with a 4.4-fold increased odds of XFS/XFG (95% confidence interval: 1.5-13.3) relative to a tortuosity score <1.0 (P-for trend=0.005).ConclusionA high degree of nailfold capillary tortuosity is a distinct non-ocular feature associated with XFS/XFG compared with either POAG or controls.

Detection of glaucoma using operator-dependent versus operator-independent classification in the Heidelberg retinal tomograph-III.

OBJECTIVE: To compare the abilities of a new Glaucoma Probability Scoring (GPS) system and Moorfields regression analysis (MRA) to differentiate between glaucomatous and normal eyes using Heidelberg retinal tomograph (HRT)-III software and race-specific databases. METHODS: In this prospective study, one eye (refractive error < or =5 D) each of consecutive normal patients and those with glaucoma was enrolled. All patients underwent a full eye examination, standard achromatic perimetry (Swedish Interactive Threshold Algorithm-standard automated perimetry (SITA-SAP), program 24-2) and confocal scanning laser ophthalmoscopy (HRT-II) within 1 month. Normal patients had two normal visual fields in both eyes (pattern standard deviation (PSD) >5% and Glaucoma Hemifield Test within 97% normal limits) and a normal clinical examination. Glaucoma was defined on the basis of SITA-SAP visual field loss (PSD<5% or Glaucoma Hemifield Test outside normal limits) on two consecutive visual fields. HRT-II examinations were exported to the HRT-III software (V.3.0), which uses an enlarged race-specific database, consisting of 733 eyes of white people and 215 eyes of black people. Race-adjusted MRA for the most abnormal sector (operator-dependent contour line placement) was compared with the global race-adjusted GPS (operator independent). MRA sectors outside the 99.9% confidence interval limits (outside normal limits) and GPS > or =0.64 were considered abnormal. RESULTS: 136 normal patients (72 black and 64 white patients) and 84 patients with glaucoma (52 black and 32 white patients) were enrolled (mean age 50.4 (SD 14.4) years). The average visual field mean deviation was (-)0.4 (SD 1.1) db for the normal group and (-)7.3 (SD 6.7) db for the glaucoma group (p<0.001). Mean GPS values were 0.21 (SD 0.23) and 0.73 (SD 0.27) for normal and glaucomatous eyes, respectively (p<0.001). Sensitivity and specificity values were 77.1% and 90.3% for GPS, and 71.4% and 91.9% for MRA, respectively. CONCLUSIONS: In this cohort, GPS software sensitivity and specificity values are similar to those of MRA, which requires placement of an operator-dependent contour line. The development of software to detect glaucoma without a contour line is critical to improving the potential use of HRT as a tool for glaucoma detection and screening.

Intraocular pressure following phacoemulsification in patients with and without exfoliation syndrome: a 2 year prospective study.

AIM: To determine the long term intraocular pressure (IOP) response to phacoemulsification in patients with and without exfoliation syndrome (XFS). METHODS: Prospective, multicentre, cohort study with the following inclusion criteria: age over 50 years, open iridocorneal angle, and cataract. Two groups were enrolled: those with XFS and those without. The main outcome was mean IOP reduction 2 years after phacoemulsification cataract extraction (PCE). Univariate and multivariate analyses were performed. RESULTS: 183 patients were enrolled, 71 with and 112 without XFS. There were 29 patients with glaucoma in both groups. Mean baseline IOP was higher in XFS compared to control eyes (17.60 (SD 3.23) mm Hg v 16.08 (3.18) mm Hg, p = 0.002). Overall IOP reduction was significantly greater in the XFS group at the 2 year time point (-1.85 mm Hg v -0.62 mm Hg in the controls (p = 0.0037)). Multivariate analysis demonstrated that the IOP lowering effect in the XFS group may be related to irrigation volume at the time of surgery. In the subgroup analyses IOP lowering was significantly greater in the XFS and XFG patients than in controls without glaucoma, and POAG controls, respectively. The percentage of patients with a postoperative IOP spike was similar and relatively high in both XFS and control groups (34% v 25%; p = 0.54). CONCLUSION: IOP decreases more in patients with XFS following PCE compared to control eyes without XFS. This effect is more pronounced in glaucoma patients and persists for at least 2 years.

Structural and functional assessment of the macular region in patients with glaucoma.

PURPOSE: To investigate the correlation of a structural measure of the macular area (optical coherence tomography (OCT)) with two functional measures (10-2 Humphrey visual field (HVF) and multifocal visual evoked potential (mfVEP)) of macular function. METHODS: 55 eyes with open-angle glaucoma were enrolled. The 10-2 HVF was defined as abnormal if clusters of > or =3 points with p<5%, one of which had p<1%, were present. The mfVEP was abnormal if probability plots had > or =2 adjacent points with p<1%, or > or =3 adjacent points with p<5% and at least one of these points with p<1%. Two criteria were used for the macular OCT: (I) > or =2 sectors with p<5% or 1 sector with p<1% and (II) 1 sector with p<5%. RESULTS: 54 of the 55 eyes showed an abnormal 10-2 HVF and 50 had central mfVEP defects. The two OCT criteria resulted in sensitivities of 85% and 91%. When both functional tests showed a defect (in 49 eyes), the OCT was abnormal in 45. For the OCT the outer and inner inferior regions were the most likely to be abnormal, and both functional techniques were most abnormal in the superior hemifield. CONCLUSIONS: Good agreement exists between macular thickness and functional defects in patients with glaucoma. Study of the macular region may provide a quantitative measure for disease staging and monitoring.

The effects of glaucoma on the latency of the multifocal visual evoked potential.

AIMS: To determine the effect of glaucomatous damage on the latency of the multifocal visual evoked potential (mfVEP). METHODS: Monocular mfVEPs were recorded from a glaucoma group (n = 50) defined by a glaucomatous disc and an abnormal visual field and a control group (n = 47). 25 patients were characterised as normal tension glaucoma (NTG) and 25 as high tension glaucoma (HTG). Monocular and interocular latency analyses of the more affected eye were obtained using custom software. RESULTS: On interocular analysis, both the HTG and NTG groups showed a statistically significant increase in mean mfVEP latency with average relative latencies and percentage of points with significant delays of 1.7 ms and 10.3% (HTG) and 1.3 ms and 8.2% (NTG) compared to -0.3 ms and 2.7% (controls). On monocular analysis, only the HTG group showed a significant increase in latency with measures of 5.7 ms and 14.6% (HTG) compared to 3.2 ms and 10.6% (NTG) and 2.1 ms and 9.6% (controls). Using the 95th percentile of a normative group as the cut off, the sensitivity ranged from 20% to 38% and the specificity from 87% to 100% with the interocular analysis providing the best discrimination, CONCLUSION: Although up to 40% of patients showed delays in the mfVEP latency, these delays were modest, on average a few milliseconds. These results differ markedly from those of a recent conventional VEP study, which reported 100% sensitivity, 100% specificity, and an average delay that exceeded 25 ms.

A New Provocative Test for Glaucoma.

PURPOSE: To compare the effects of the water-drinking test (WDT) with the 30° inverted body position test on intraocular pressure (IOP) in normal patients, suspected glaucoma patients and glaucoma patients. MATERIALS AND METHODS: Based on clinical evaluation of the optic disk, IOP, and standard achromatic perimetry (SAP) of 71 eyes, 18 were "normal" (normal SAP and optic disk evaluation, and IOP < 21 mm Hg), 30 were "glaucoma suspect" (GS; normal SAP, cup/disk (C/D) ratio > 0.5 or asymmetry > 0.2 and/or ocular hypertension), and 31 had "early glaucoma" (MD < -6 dB, glaucomatous optic neuropathy). Standard achromatic perimetry was performed with the Octopus 3.1.1 Dynamic 24-2 program. Patients fasted before the WDT, and four measurements were performed at basal, 15', 30, and 45' after drinking 1 liter of water (WDT) in 5 minutes. In the 30° inverted position, IOP measurement with Perkins applanation tonometer was taken after 5 minutes lying down. RESULTS: There was a statistical difference in all groups between the basal IOP and peak IOP during the WDT (p < 0.001) and in the inverted position IOP (p < 0.001). Controls (p = 0.50), suspects (p = 0.41) and glaucoma patients (p = 1.0) did not exhibit a difference between WDT-IOP and inverted position IOP. CONCLUSION: The 30° inverted position test was as efficient as WDT in detecting peak IOP. This new provocative test is easier, faster and more comfortable for both patients and doctors. How to cite this article: Kanadani FN, Moreira TCA, Campos LF, Vianello MP, Corradi J, Dorairaj SK, Freitas ALA, Ritch R. A New Provocative Test for Glaucoma. J Curr Glaucoma Pract 2016;10(1): 1-3.

Studies of human uveal melanocytes in vitro: growth regulation of cultured human uveal melanocytes.

PURPOSE: The authors studied the growth requirements and growth regulation of cultured human adult uveal melanocytes (UM). METHODS: The effect of various mitogens and growth factors on the growth of UM were tested separately or combined on cultured UM in multiwell plates. RESULTS: Basic fibroblast growth factor (bFGF) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) stimulate the growth of UM. Without these agents, the UM did not grow or survive. A cyclic adenosine monophosphate (cAMP) stimulator, such as isobutylmethylxanthine or cholera toxin, stimulated growth in the presence of bFGF. Fetal bovine serum (FBS) is also required for growth. In its absence, UM did not grow, even in the presence of bFGF and cAMP stimulators. Other substances, such as epidermal growth factor, acidic FGF, nerve growth factor, and platelet-derived growth factor had no stimulating effects on the growth of UM. CONCLUSIONS: Three classes of agents are required for the growth of UM in vitro: bFGF or TPA, a cAMP stimulator, and FBS. Adult human UM cultured in medium containing all these agents grew well and could be passaged for many generations.

Measurement of ultrasound biomicroscopy images: intraobserver and interobserver reliability.

PURPOSE: To evaluate intraobserver and interobserver reproducibility of measurement of images obtained during ultrasound biomicroscopy. METHODS: Four anterior segment images of four normal patients were obtained by a single examiner. The measurements of three independent observers were compared to assess interobserver reproducibility in quantifying the images. Thirteen different anterior segment parameters were measured by each observer on each image. Intraobserver and interobserver reproducibility of measurement were assessed by calculating the coefficient of variation for each individual observer and by using the F test to detect a difference among observers. RESULTS: Intraobserver reproducibility was high. Interobserver reproducibility for the measured parameters varied considerably and was affected by subjective interpretation of visualized anatomic landmarks. CONCLUSIONS: The optimal parameters for quantitative ultrasound biomicroscopy require refinement. Measurements of alterable parameters are best measured presently by a single observer. Ultrasound biomicroscopy has the potential to elucidate anatomic relationships underlying much anterior segment disease, but caution in interpreting quantitative differences is warranted.

Isolation and cultivation of human iris pigment epithelium.

There have been very few attempts to isolate and culture human iris pigment epithelium (IPE). Earlier efforts that used whole iris explant methods did not achieve pure cultures of IPE. We have developed methods for separating the IPE from the iris stroma of post-mortem eyes that avoid contamination by other cell types. Three different isolation methods were studied: direct dissection, enzyme digestion, and enzyme-assisted microdissection. The latter method yielded the best results. After treatment with enzyme solution, the IPE was easily separated from the stroma under the stereomicroscope and subsequently cultured with supplemented F12 medium. With this method, approximately 2.3 x 10(5) cells were isolated from each iris with an average viability of 90.2%. IPE cells isolated from 19 of 24 eyes grew to confluence in primary culture. The IPE could be maintained in pure culture for many generations over several months with up to 20 population doublings. Cultured IPE demonstrated cytokeratin and S-100 protein by immunocytochemistry. Some of these cells also displayed desmin, indicating origin from the anterior IPE. Cultured IPE cells retained most of the characteristics of IPE in vivo, such as apical/basal polarization, microvilli, and many cell junctions. Gradual dilution of pigment occurred in the dividing IPE cells, suggesting an inability to produce melanin in vitro. A subpopulation of the IPE cells contained myofilaments by electron microscopy, also indicating a anterior IPE origin. This method provides a source for large numbers of human IPE cells and could be useful in studies of the biology of IPE and the role of IPE in pathogenesis of several eye diseases, most notably exfoliation syndrome and its associated glaucomas.

The combined effect of brain-derived neurotrophic factor and a free radical scavenger in experimental glaucoma.

UNLABELLED: PURPOSE. Brain-derived neurotrophic factor (BDNF) had a limited effect on the survival of retinal ganglion cells (RGCs) in rats' eyes with elevated intraocular pressure (IOP). The combined treatment of BDNF and a nonspecific free radical scavenger N-tert-butyl-(2-sulfophenyal)-nitrone (S-PBN) was investigated on the RGCs in hypertensive eyes of rats. METHODS: Adult Wistar rats were separated into five groups: BDNF (0.5 microg) + S-PBN; BDNF (1. 0 microg) + S-PBN; BDNF (1.0 microg); S-PBN; and phosphate-buffered saline. Right eyes served as normal controls (n = 10). RGCs were labeled with 5% Fluoro Gold; injected into the superior colliculus. Three days after intratectal injection, the episcleral veins of the left eyes were cauterized. Intravitreal injection of BDNF was performed on days 5, 13, 21, and 29 after IOP elevation. S-PBN was injected intraperitoneally (100 mg/kg body wt) every 12 hours starting 30 minutes after cauterization. RESULTS: The survival of RGCs using BDNF treatment alone in moderately hypertensive eyes and systemic administration of S-PBN alone did not significantly rescue the RGCs. However, the combination of BDNF and S-PBN increased the survival of RGCs to 90.1%. CONCLUSIONS: Trophic factors and antioxidants have synergistic effects on rescuing RGCs from death in eyes with elevated IOP. Further studies of different combined treatment therapies may provide avenues to save RGCs from death in eyes with elevated IOP.

Ultrastructure of the eye in fetal type II glycogenosis (Pompe's disease).

Type II glycogenosis is an autosomal recessive storage disease characterized by absence of the enzyme acid alpha-1,4-glucosidase. The eye of a 16 week fetus, aborted after diagnosis by amniocentesis, was studied by light and electron microscopy. Extensive deposits of lysosomal and cytoplasmic glycogen were present in virtually all ocular tissues examined, with the notable exception of pigment epithelia (iris and retina). The massive glycogen deposits present in this, the youngest case thus far examined histologically, emphasize the involvement of the fetus from its earliest stages and the importance of prenatal diagnosis.

Studies of human uveal melanocytes in vitro: isolation, purification and cultivation of human uveal melanocytes.

PURPOSE: To develop the methods for isolation and cultivation of human uveal melanocytes (UM) from adult donor eyes. METHODS: After removal of the pigment epithelium, the uvea was pretreated in trypsin solution at 4 degrees C overnight, incubated at 37 degrees C with trypsin for 1 hr, then incubated with collagenase for 3 hr. Released cells were collected each hour during the incubation and cultured with F12 medium supplemented with fetal bovine serum, basic fibroblast growth factor, isobutylmethylxanthine and cholera toxin. Contaminant cells were eliminated by adding a selective cytotoxic agent, geneticin, when necessary. RESULTS: These methods provide pure melanocyte cultures with high cell yields, good viability, and rapid growth rates. UM isolated and maintained using these methods can be passaged 23 times for a period of 7 mo for more than 35 population doublings. This is comparable to results obtained with cultured neonatal dermal melanocytes and exceeds results obtained with adult dermal melanocytes cultured in media supplemented with phorbol ester, isobutylmethylxanthine, and cholera toxin. CONCLUSION: A method for isolation and cultivation of UM has been developed that yields satisfactory results. Cultured UM may be useful in in vitro studies of UM physiology and may allow development of in vitro models of the pathogenesis of uveal malignant melanoma.

Human trabecular meshwork cells in culture: morphology and extracellular matrix components.

This study demonstrates the presence of laminin and collagen type IV in the extracellular space of human trabecular meshwork (HTM) cells in culture and its absence in cultures of fibroblasts from sclera adjacent to the outflow pathway. These basement membrane components can be detected by standard immunohistochemical techniques. Positive staining for these macromolecules is found only after the HTM cells have reached confluence. The presence of laminin and human collagen type IV in the early passages can serve as additional criteria for identification of HTM cells in culture. These cells provide a useful experimental system for studying the effects of drugs and other factors on the synthesis of components of the extracellular matrix.

S (blue) cone pathway vulnerability in retinitis pigmentosa, diabetes and glaucoma.

A variety of retinal disease lead to a decrease in the sensitivity of the S (blue) cone pathways. To determine the possible sites and mechanisms of this loss we compared the sensitivities of an S (blue/pi-1) and an M (green/pi-4) cone pathway in patients with retinal diseases that differ as to their primary locus of sensitivity loss. The sensitivities of an S and an M cone pathway were assessed in patients with retinitis pigmentosa, insulin-dependent diabetes mellitus and open-angle glaucoma using Stiles two-color increment threshold technique. A greater loss in sensitivity of an S than an M cone pathway was found for all three disease groups; however, the diabetic patients showed a more selective loss. The results suggest that multiple sites are involved and that the combined effects of metabolic abnormalities and hypoxia contribute to the selective loss.

An attempt to detect glaucomatous damage to the inner retina with the multifocal ERG.

PURPOSE: To detect glaucomatous damage to the inner retina using the multifocal electroretinogram (mERG). METHODS: The stimulus array consisted of 103 hexagons with a mean luminance of 100 cd/m2 and a contrast of 50%. The mERG was recorded from 13 control subjects, 18 patients with open-angle glaucoma (OAG), 4 glaucoma suspects, and one patient with ischemic optic neuropathy (ION). Individual responses, as well as responses summed within quadrants or across the entire array, were measured in a number of ways. Humphrey visual fields were obtained for all patients, and the mean total deviation (MD) values for the 18 patients with OAG ranged from -2.2 to -18.2 with a mean (SD) of -7.3 (4.5). RESULTS: The mERG measure that best discriminated between the patients and the control subjects was the ratio of the amplitude at 8 msec after the peak response to the amplitude at the peak. Although the value of this ratio fell below the median of the control group for 16 of the 18 OAG patients, only 6 of these patients had ratios that fell below the normal range. Other measures of first- and second-order kernels did not do as well. Both within and across patients, the correlation between local field loss and the mERG ratio measure was poor. Furthermore, although in some patients the mERG waveform is clearly different from normal, in other patients (including the patient with ION) the waveform approximates the normal even in visual field areas with substantial sensitivity loss. CONCLUSIONS: Because glaucomatous damage is known to affect the ganglion cell axon, these data suggest that damage to ganglion cell axons is not a sufficient condition to produce changes in the mERG as measured here and that in patients with clear changes in mERG waveforms, these changes do not appear to be well localized and local waveforms are poorly correlated with local changes in field sensitivity.