Unilateral testing of utricular function

PURPOSE: To examine acquired pit of the optic nerve as a risk factor for progression of glaucoma. METHODS: In a retrospective longitudinal study, 25 open-angle glaucoma patients with acquired pit of the optic nerve were compared with a group of 24 open-angle glaucoma patients without acquired pit of the optic nerve. The patients were matched for age, mean intraocular pressure, baseline ratio of neuroretinal rim area to disk area, visual field damage, and duration of follow-up. Serial optic disk photographs and visual fields of both groups were evaluated by three independent observers for glaucomatous progression. RESULTS: Of 46 acquired pits of the optic nerve in 37 eyes of 25 patients, 36 pits were located inferiorly (76%) and 11 superiorly (24%; P < .001). Progression of optic disk damage occurred in 16 patients (64%) in the group with acquired pit and in three patients (12.5%) in the group without acquired pit (P < .001). Progression of visual field loss occurred in 14 patients (56%) in the group with acquired pit and in six (25%) in the group without pit (P=.04). Bilateral acquired pit of the optic nerve was present in 12 patients (48%). Disk hemorrhages were observed more frequently in the group with acquired pit (10 eyes, 40%) compared with the group without pit (two eyes, 8%; P=.02). CONCLUSION: Among patients with glaucoma, patients with acquired pit of the optic nerve represent a subgroup who are at increased risk for progressive optic disk damage and visual field loss.     

Evaluation of coexisting optic nerve head drusen and glaucoma with optical coherence tomography

OBJECTIVE: Optic nerve head drusen often make evaluation of the nerve head difficult to interpret. In addition, visual field defects are known to occur in patients with optic disk drusen, resembling glaucomatous damage. The authors report two cases of coincident optic nerve head drusen and glaucoma, in which the use of optical coherence tomography (OCT) in evaluating the nerve fiber layer was beneficial. PARTICIPANTS: Two patients with both optic nerve head drusen and glaucoma, one with primary open angle glaucoma, the other with pseudoexfoliation glaucoma were evaluated. Both patients had asymmetric optic disk drusen, with clinically visible drusen only in one eye. INTERVENTION: Ophthalmologic examination, color and red-free photography, automated Humphrey visual field testing and OCT were performed. RESULTS: Nerve fiber layer loss as measured by OCT was found to be greater than expected by the appearance of the optic nerve head and red-free photography, with visual fields consistent with findings in case 1. In case 2, visual fields were full, despite nerve fiber layer thinning seen by OCT and red-free photography. CONCLUSIONS: There can be significant nerve fiber layer thinning in patients with both glaucoma and optic disk drusen, despite the appearance of the optic nerve head in these patients. The cup margin may be obscured by the drusen, giving rise to a falsely full-appearing disk. In such cases, OCT may provide a useful means to quantitatively measure the nerve fiber layer thickness and to aid in the management of these patients by detecting nerve fiber layer thinning earlier than would otherwise be possible.     

Pattern-reversal electroretinogram in response to chromatic stimuli: II. Monkey

We have recorded steady-state PERGs from five macaque monkeys in response to red-green plaid patterns reversed sinusoidally in contrast. The patterns had either a pure luminance contrast (red-black, green-black, yellow-black), pure red-green color contrast, or a variable amount of luminance and color contrast. By varying the relative luminance of the red-to-total luminance (color ratio) of red-green patterns, a value could be obtained at which the PERG amplitude was either minimum or locally maximum, and the phase was most lagged. This value was very similar to that producing equiluminance in human observers, and was considered to be equiluminance for the monkey. The phase of the PERG to chromatic stimulus was systematically lagged compared with that of luminance stimuli, by an amount corresponding to about 10-20 ms under our experimental conditions. The variation of phase with temporal frequency suggested an apparent latency of about 80 ms for color contrast compared with 63 ms for luminance. These estimates were confirmed with separate measurements of transient PERGs to abrupt contrast reversal. As a function of temporal frequency, the chromatic PERG function was clearly low-pass with a cutoff around 15 Hz, whereas that to luminance was double-peaked and extended to higher temporal frequencies, around 30 Hz. For both luminance and chromatic stimuli, the amplitude of PERGs increases with increasing stimulus contrast. By summing vectorially the luminance and chromatic responses of appropriate contrasts, we were able to predict with accuracy the response as a function of color ratio. In two monkeys, the optic chiasm was sectioned sagittally causing total degeneration of ganglion cells in the nasal retina, without affecting the temporal retina (verified by histology). In these animals, there was a strong response to both luminance and chromatic patterns in the temporal retinae, but none to either type of pattern in the nasal retinae, suggesting that the PERG to both luminance and chromatic stimuli arises from the inner-retinal layers. Electrophysiological studies suggest that the PERG to chromatic stimuli is probably associated with the activity of P-cells. P-cells may also make a major contribution to the PERG of luminance stimuli, although M-cells may also participate. The above findings on normal monkeys all agree with those reported in the accompanying paper for humans (Morrone et al., 1994), so similar conclusions can probably be extended to human PERG.     

Optic disk appearance in ocular hypertensive eyes

We examined the optic disk appearance in ocular hypertensive eyes that had a normal result of conventional computed perimetry. Color stereo-optic disk photographs of 104 ocular hypertensive subjects and of 216 normal individuals were morphometrically evaluated. In the ocular hypertensive eyes as compared to the normal eyes, significant differences (P < .0001) were detected for a smaller area and an abnormal shape of the neuroretinal rim, larger zones alpha and beta of the parapapillary chorioretinal atrophy, a decreased visibility of the retinal nerve fiber layer, and a higher frequency of localized nerve fiber layer defects. The variables most useful to indicate optic nerve damage were an abnormal shape of the neuroretinal rim and a decreased visibility of the nerve fiber layer. The most specific variable was the presence of localized retinal nerve fiber layer defects. Evaluation of these variables may be helpful for the early diagnosis of glaucoma.     

Evaluation of the retinal nerve fiber layer

In normal eyes, the retinal nerve fiber layer (RNFL) is usually best visible in the inferior temporal part of the fundus, followed by the superior temporal region, the nasal superior region and the nasal inferior region. This distribution correlates with the configuration of the neuroretinal rim, the diameter of the retinal arterioles, the location of the foveola, and the lamina cribrosa morphology. With increasing age, the RNFL visibility decreases diffusely without preferring special fundus regions and without the development of localized defects. With all optic nerve diseases, the visibility of the RNFL is decreased in addition to the age-related loss, in a diffuse and/or a localized manner. The localized defects are wedge-shaped and not spindle-like defects, running toward or touching the optic disk border. Typically occurring in about 20% of all glaucoma eyes, they can be found also in other ocular diseases, such as optic disk drusen, toxoplasmotic retinochoroidal scars, longstanding papilledema or optic neuritis due to multiple sclerosis. Since they are not present in normal eyes, they almost always signify an abnormality. RNFL evaluation is especially helpful for early glaucoma diagnosis and in glaucoma eyes with small optic disks. In advanced optic nerve atrophy, other examination techniques, such as perimetry, may be more helpful for following optic nerve damage. Considering its great importance in the assessment of optic nerve anomalies and diseases and taking into account the feasibility of its ophthalmoscopic evaluation using green light, the retinal nerve fiber layer should be examined during any routine ophthalmoscopy.     

Electrophysiological signs of retinal dopamine deficiency in recently diagnosed Parkinson's disease and a follow up study

Electrophysiological studies, including electrooculogram (EOG), and simultaneously recorded flash and pattern evoked electroretinograms (FERG and PERG) and visually evoked potentials (FVEP and PVEP) were made in 1988 on 10 newly diagnosed untreated Parkinson's patients at Stage 1 of the Hoehn and Yahr scale. Follow up studies were made on five out of the 10 patients when their disease had progressed to Stage 2 during 1993. The earliest and only sign of abnormality detected in the Stage 1 of Parkinson's patients in 1988 was a delay in the time to reach the peak light rise in the EOG. When the disease had progressed to Stage 2, not only a delay in the time to reach the peak light rise but also a reduction in the amplitude of the peak light rise in the EOG, together with changes in PERG, FERG and PVEPs were demonstrable. These changes observed in PERG, FERG and PVEPs were generally consistent with those reported by previous studies. It is suggested that the reason for the susceptibility of pigment epithelial function to dopamine deficiency in Parkinson's disease may be due to the pigment epithelium being at the extremity of the diffusion pathway from dopamine release sites at the inner plexiform layer.     

Lymphocyte recirculation, exercise, and immune responses

OBJECTIVES: Visual evoked potentials (VEPs) show abnormal responses in newly-diagnosed insulin-dependent diabetic (IDDM) patients. Electrophysiological methods allow one to dissect and explore different structures contributing to neural conduction in the visual pathways. The aim of our work was to assess whether the VEP abnormalities are due to impaired function of the retinal layers and/or a delayed conduction in the postretinal visual pathways. METHODS: Simultaneous recordings of VEP and pattern-electroretinogram (PERG) were performed at two intervals (at entry of the study and after 3 months) in 14 newly-diagnosed IDDM patients (age: 24.8+/-6.8 years; duration of disease: 3+/-1.5 months), and in 14 age-matched control subjects. RESULTS: In comparison with control subjects, IDDM patients showed: VEP P100 latencies significantly delayed (P < 0.01), a significant impairment of all PERG parameters (P < 0.01) and retinocortical time (RCT, difference between VEP P100 and PERG P50 latencies) and latency window (LW, difference between VEP N75 and PERG P50 latencies) also significantly increased (P < 0.01). All electrophysiological parameters were not significantly changed when retested after 3 months. No correlations were found between VEP P100 latency, RCT, LW and PERG parameters. CONCLUSIONS: Impaired PERG indicates an involvement of the innermost retinal layers; increased values of RCT and LW represent an index of delayed neural conduction in the postretinal visual pathways. Therefore two sources, one retinal (impaired PERG) and one postretinal (delayed RCT and LW), may independently contribute in to the abnormal responses of VEP observed in newly-diagnosed IDDM patients. Three months of relatively-stable metabolic control have not normalized the VEP and PERG impairment.     

Individual variability in the diurnal intraocular pressure curve

BACKGROUND: Reduction of intraocular pressure (IOP) is a primary goal of most glaucoma treatments. However, because the IOP varies during the day, single measurements performed in an ophthalmologist's office do not necessarily provide information on the peak level and fluctuation of the IOP. METHODS: Home tonometry was performed to gain more information on the nature of the diurnal IOP curves and on their variability. One hundred seventy-six patients with open-angle glaucoma (OAG), 55 subjects with ocular hypertension (OHT), and 18 control individuals measured their IOP five times daily at home for 4 to 8 consecutive days using a self-tonometer. RESULTS: Well-defined diurnal IOP variations were observed in all three groups with a predominance of curves with morning or mid-day maxima. Erratic IOP curves without a diurnal rhythm were present in OHT (22%) and OAG (16%) patients but not in control subjects. Differences between the curves of the two eyes of an individual were frequent in OHT (33%) and OAG (36%) patients but not in control subjects (6%). Finally, the majority of OHT (72%) and OAG (66%) patients showed a difference in their diurnal curve patterns on repeat home tonometry performed months apart. CONCLUSION: The authors indicate that it is difficult to rely on one eye as a control for the other. They also indicate that changes in IOP observed in the office at different visits often may be due to a shift in the type of diurnal curve rather than to a true change in the mean IOP. Monitoring of the diurnal IOP may be necessary in some cases if the clinician relies, even partially, on the level of IOP when making a decision on patient management.     

D1 agonist CY208-243 attenuates the pattern electroretinogram to low spatial frequency stimuli in the monkey

We investigated whether or not the D1 agonist, CY 208-243, affects the spatial tuning function of pattern electroretinogram (PERG). Two lightly anaesthetised monkeys were studied before and after CY 208-243 or placebo administration. The results show that the PERG response to 0.5 cycles/degree (c/d; coarse), but not to 2.3 c/d (medium) spatial frequency stimuli disappears following systemic administration of this drug. Since previous results show that D2 blockers attenuate the PERG only above 2.3 c/d, foremost the peak of the normal spatial frequency response function, the current results suggest that dopamine itself, via D1 receptors, may be responsible for the low spatial frequency decline of normal spatial PERG tuning function. We infer that the synergistic activation of D1 and D2 receptors is needed to shape the spatially tuned primate ERG.     

Studies on the profile of immunostimulant activities of modified iridoid glycosides

PURPOSE: To determine the prevalence of and risk factors for superior segmental optic nerve hypoplasia in offspring of mothers with type I diabetes mellitus. METHODS: Thirty-four subjects aged between 4 and 37 years, the children of 23 mothers who had type I diabetes mellitus at the time of pregnancy, aged between 4 and 37 years, were recruited from one institution and prospectively examined in search of an optic disk-related anomaly. RESULTS: Of the 34 subjects, three females (8.8%) showed classic ophthalmoscopic and perimetric features of superior segmental optic nerve hypoplasia, bilateral in two patients and unilateral in one. Pregnancies leading to affected children showed a tendency to be shorter, birth weight to be lower, and control of maternal diabetes mellitus to be poorer compared with pregnancies resulting in unaffected children. No variable unique to the affected subjects as opposed to the unaffected majority could be identified. CONCLUSIONS: We found a superior segmental optic nerve hypoplasia, described as a "topless disk," in three of 34 subjects (8.8%) at risk for this condition. Topless disk thus seems to be more common than was previously thought, possibly having been missed because of its subtle signs and only mild impairment of visual performance in affected individuals. Female sex, short gestation time, low birth weight, and poor maternal diabetes control may represent additional risk factors for the development of a topless disk. Its pathogenesis remains obscure, but the responsible pathogenic event may occur in the perinatal period.     

Change in the land vertebrate community under new conditions in nature]

PURPOSE: To report bilateral congenital optic nerve head pits in monozygotic siblings. METHOD: Case reports. RESULTS: Pits were found in abnormally large optic disks in both eyes of two otherwise healthy female monozygotic siblings aged 15 years. Pit size increased and visual acuity decreased with increased optic disk area. In one eye, nonrhegmatogenous retinal detachment developed that eventually necessitated pars plana vitrectomy. The siblings' parents were unremarkable. CONCLUSIONS: Congenital optic nerve head pits can occur bilaterally in otherwise healthy monozygotic siblings with ophthalmologically unremarkable parents. Associated nonrhegmatogenous retinal detachment may be treated by pars plana vitrectomy. Pit size is positively correlated with disk area.     

The persistent trigeminal artery in vascular brain diseases]

Symptoms of primary open-angle glaucoma can be divided into main and accessory and risk factors. The main symptoms are increased intraocular pressure and changes in the visual field and optic disk characteristic of glaucoma. The accessory symptoms and risk factors are a family history of glaucoma, diabetes mellitus, myopia, poor discharge of aqueous humor, pseudoexfoliative syndrome, elements of goniodysgenesis and depositions of pigmented granules in the anterior chamber corner, and asymmetric intraocular pressure, humor discharge, and extent of optic disk excavation. Causes and diagnosis of nonglaucomatous hypertension and normal-pressure glaucoma are discussed.     

Diabetic papillopathy: two case reports in individuals with adult onset diabetes mellitus

BACKGROUND: Diabetic papillopathy is a benign unilateral or bilateral optic neuropathy with transient optic disk edema and minimal reduction in visual function. The optic disk edema typically resolves in a few months with no resulting optic atrophy and minimal or no decrease in acuity. The exact etiology of the disk edema is unknown, but theories include retinal vascular leakage into and surrounding the optic nerve and disruption of axoplasmic flow resulting from microvascular disease of the optic nerve head vasculature. CASE REPORTS: Two adult patients receiving insulin for type II diabetes mellitus manifested bilateral disk edema and minimal visual dysfunction. Both patients showed funduscopic evidence of mild-to-moderate nonproliferative diabetic retinopathy O.D. and O.S., and one patient had clinically significant macular edema in both eyes. The diagnosis in both cases was diabetic papillopathy. Both patients had significant resolution of their disk edema in 3 to 6 months, with stable acuities and no signs of optic atrophy. CONCLUSIONS: Although diabetic papillopathy is a well-known clinical entity in patients with type I diabetes, the clinical profile can be expanded to include individuals with type II diabetes.     

Optic nerve compression by carotid arteries in low-tension glaucoma

Low-tension glaucoma (LTG) is manifested by glaucomatous optic nerve damage and visual field loss despite normal intraocular pressure (IOP). We describe 62 patients with classical signs of LTG. Computed tomography (CT) was performed in all patients. In 56 of the patients (90.3%), pathology of the intracavernous carotid arteries adjacent to the intracranial opening of the optic canal could be demonstrated. In 28 patients (45.2%) a clear asymmetry of the optic nerve cupping was found and could be correlated with the severity of the carotid artery pathology. A control group of 24 age-matched patients included five (20.8%) with intracavernous carotid artery calcification and only one (4.2%) with intracavernous ectasia. We suggest that calcification, dilatation and ectasia of the carotid artery into the optic canal may play an important role in the pathogenesis of many cases of LTG. The close proximity of the carotid artery to the optic nerve at this location may result in compressive neuropathy with subsequent glaucomatous damage of the optic nerve head.     

Glaucomatous cupping of the optic disk by ultrasonography

B-scan ultrasonography was used to evaluate advance glaucomatous cupping of the optic disk (0.7 cup/disk ratio or greater) in one normal subject and six patients with glaucoma. The normal eye emitted a continuous echo from the posterior pole, which conformed to its mild degree of concavity. The glaucomatous eyes emitted echos from the posterior pole, demonstrating the more extreme concavity of the optic cup. Ultrasonographic evaluation of an acrylic plate containing holes of known diameter demonstrated the limits of resolution and artifacts that resulted from this examination.     

Bilateral optic disk pallor after unilateral internal carotid artery occlusion

Bilateral pallor of the optic disks was observed in a 52-year-old man after dissection of an internal carotid artery. Diffuse pallor of the ipsilateral optic disk reflected infarction of the ipsilateral optic nerve and "bow-tie" atrophy of the contralateral optic disk reflected infarction of the ipsilateral optic tract. The findings were due to an occlusion of the internal carotid artery proximal to the origin of the ophthalmic artery, resulting also in insufficiency in the area of supply of the anterior choroidal artery.     

Perifollicular clear space under skirt-like epithelial structure of human small vellus hair follicle

Peak latencies of pattern electroretinogram (PERG) were compared between glaucomatous eyes and non-glaucomatous eyes. Contrast threshold for motion perception (CTMP) was also measured with a new device in addition to routine static contrast sensitivity, static visual field and visual acuity. In the present recording, configurations for PERG, i.e. low reversal rate, low mean luminance and presence of background illumination, the PERG peak and trough (P1 and N2, respectively) latencies, were significantly prolonged in the glaucomatous eyes. Although both of the two PERG latencies were strongly correlated with the CTMP, only the P1 peak latency was strongly correlated with the perimetric indices. These results suggest that the P1 and N2 latencies reflect different aspects of signal processing in the retina, especially for moving targets.     

The effect of immunotoxins directed against CD80 and CD86 on primary T-cell alloresponses

A 13-year-old boy presented with acute loss of vision in his right eye of 2 weeks' duration. He had a high fever and was ill for several days, then improved but suffered recurrent episodes of sweating and a high fever. Ophthalmoscopy of the right eye showed optic disk edema, mild vitreous cells, and minimal exudates in the macula. Bartonella henselae titers were positive. A diagnosis of optic disk edema with a macular star secondary to cat-scratch disease was made. The patient was treated with doxycycline and made a dramatic improvement to visual acuity of 20/30 with a minimal residual relative central scotoma. The optic disk edema and macular star resolved, and the patient was left with mild optic atrophy in the right eye.     

Retinal dopamine depletion in young quail mimics some of the effects of ageing on visual function

The hypothesis that retinal dopaminergic (DA) neurones are involved in the visual functions of interest was tested. The retinal DA in young quail was partially depleted by intravitreal injection of 6-hydroxydopamine (6-OHDA). It was found that the refractive state of 6-OHDA-treated birds became more myopic than normal (untreated) young, whereas the pupil diameter was not affected. The contrast sensitivity of 6-OHDA treated quail was significantly lowered (two to three times) at all spatial frequencies studied (0.25-5 c/d), and the peak latency of pattern electro-retinogram (PERG) response was prolonged by 3-4 msec (9%). Furthermore, the visual acuity and maximal amplitude of PERG response of the 6-OHDA-treated young quail were lower than those of normals. From histochemical studies, it was revealed that the morphology of the DA cells of 6-OHDA-treated young appeared similar to those of the old quail; the DA cells of 6-OHDA-treated retinae were less fluorescent and 2.5-5 times less numerous than respective controls. Combining the PERG and the morphological results, it would seem that the retinal DA plays an important role in the visual functions studied, and that loss of retinal DA could underlie some of the visual changes which occur during ageing.