Some aspects of cataract morphology: A SEM-study

Two lenses from patients of very advanced age with senile cataracts were processed for SEM, fractured equatorially, sputtered with Au and examined by SEM. In the cross-fracture various areas could be observed. Although the overall structure of the lens-fibres appeared to be intact, higher magnifications showed that the len-fibre material had changed into a brittle structure, with either a granular appearance or a fibrillar character. At other places clearly recrystallization of lens-fibre proteins had taken place, with the formation of finger-like substructures, sometimes organized into plate-like structures or running parallel to each other in a kind of undulating pattern.Between the various areas of chemically changed lens-fibre material certain canal-like areas were found with cellular structures, the so-called waterclefts or Wasserspalten. Structures which, together with the chemical change in the lens proteins, account for the dramatic change in light dispersion.The work was carried out at the Centre for Medical Electron Microscopy, 69/2 Oostersingel, 9713 EZ Groningen.     

Epidemiological aids to clinical decision making in primary open angle glaucoma

We have described the epidemiological analysis of one aspect of the King's College Hospital computerised data base; namely initial intraocular pressure as an indicator of visual field loss. The methods involved the use of the four-fold table to determine sensitivity and specificity at different pressure levels. From these results (1) the changes in the pre and post test probability of field loss are calculated and (2) a sensitivity/specificity trade off curve or decision curve is constructed. In this way the optimal cut-off level or operating point for a population of specific type and composition can be determined. The factors concerned in decision making are always complex but such an approach allows a rational and quantifiable alternative to reliance on clinical impression and intuition. The results have significance in relation to decisions on the management of patients and on population screening programmes for glaucoma.     

Background light adaptation of the retinal neuronal adaptive system. II. Dynamic effects

The dynamic effects of continuous exposure to light on the neuronal adaptive system of the retina, as indicated by the oscillatory response (OPs) of the electroretinogram (ERG) were studied in the albino rat. Digitally filtered OPs and the a- and b-waves of the corneal ERG were simultaneously recorded in dark adaptation, during continuous light adaptation to four levels of background light (BGL) changing in steps of two log units from 1.43×10^–6cd/m², referred to as low and high scotopic, low and high mesopic levels. Exposed to high scotopic BGL the total oscillatory response (SOP) significantly enhanced within the first minute, whereas the amplitudes of the a- and b-waves were unaffected. In low mesopic BGL the SOP increased within the first minute, whereas the a- and b-waves significantly decreased. High mesopic BGL instantaneously and profoundly reduced both the SOP and the slow potentials. The individual OPs changed in amplitudes mainly within the first minute of BGL. In general, the earlier OPs (O1 and O2) reacted more to the two scotopic BGL levels, whereas the later OPs (O3 and O4) were more affected by the relatively brighter two mesopic conditions. In conclusion, the rapid increase of the OPs within the first minute of high scotopic and low mesopic BGL exposure may represent a rudimentary light adaptational effect in the rod-dominated rat retina. These findings also suggest that the neuronal adaptive mechanism of the retina seems to be a robust system, probably attaining preservation of visual abilities in the rat on exposure to light.     

Cyclosporine-A in the treatment of serpiginous choroiditis

Summary Seven patients affected by bilateral inflammatory serpiginous choroiditis have been treated with Cyclosporine-A for 6-21 months. Nine outof the fourteen eyes showed a significant improvement in their visual acuity; five eyes did not change.Cyclosporine-A may, therefore, be considered effective in the treatment of this disease.Its usefulness seems to be greater when the serpiginous choroiditis is in its acute stage; chronic stages, however, also seem to improve under treatment.Its main indication is, in our opinion, the involvement of the macular region of the second eye, when the first eye is already damaged. We consider Cyclosporine-A, in these situations, to be a first choice treatment.     

Electrophysiological evidence that early glaucoma affects foveal vision

The pattern electroretinogram (PERG) and visual evoked potential (PVEP) were recorded simultaneously using a 1.1 cpd pattern which was counterphase modulated at 1 Hz. The responses of ocular hypertensive (OHT) eyes (with normal visual fields) and eyes with early glaucoma (with early visual field defects and/or early cupping of the optic nervehead) were compared to age-matched normal observers. All patients (26 eyes) and normal observers (14 eyes) had normal transient flash electroretinograms. Delays were seen in mean PERG latency in both OHT and early glaucoma eyes, while mean PERG amplitude was significantly reduced only in the early glaucoma eyes. The PVEP responses were unmeasurable in 11/26 patient eyes because the waveforms were grossly abnormal in shape, making it impossible to identify the N- and P-components. The data were categorized in this manner: a patient response was considered abnormal if latency or amplitude exceeded normal limits (PERG or PVEP) or if the waveform was unmeasurable due to its shape (PVEP only). Of the 26 patient eyes, we found that 8 eyes had normal PERG and PVEP, 11 eyes had abnormal PERG and PVEP, one eye had an abnormal PERG and a normal PVEP, and 6 eyes (3 patients) had a normal PERG and an abnormal PVEP. These data support the proposition that foveal vision (as assessed by the PVEP) may be affected by early glaucomatous damage. The relationship between the PERG and PVEP also was evaluated using a new measurement which we call the latency window. Using this measurement, 15/26 patient eyes were abnormal - 9 of these had unmeasurable PVEPs. This measurement could be useful in classifying W-shaped PVEPs as normal or abnormal.This study was supported in part by Grants EY01708 and EY01867 from the National Eye Institute, Bethesda, MD, by Fight For Sight Grant-in-Aid G-274, and by an unrestricted grant from Research to Prevent Blindness, Inc., New York, NY.     

Oculokinetic perimetry compared with standard perimetric threshold testing

To calibrate oculokinetic perimetry (OKP) as developed by Damato in terms of conventional perimetric threshold values, 33 eyes with either glaucoma or ocular hypertension were tested with a standard Humphrey Field Analyzer using the Central 30-2 test and twice with a 26-point OKP chart. The frequency of seeing of the OKP test spot was plotted against 30-2 thresholds. This showed a weak relation between the two tests. Subsequently eyes that were considered to have had poor fixation were omitted, but false positive and false negative results still occurred in 19 remaining eyes. To check whether Troxler's effect (local adaptation) might have caused false positives, 6 subjects were tested with OKP, controlling the fixation times. Increasing the fixation time from very short to 2 and 5 seconds yielded more not seen responses in OKP. False negative data were found to occur preferentially in border areas of visual field defects. The average frequency of seeing curve over all data showed a 50% frequency of seeing for the OKP stimulus at a 14.6 dB equivalent conventional threshold value. The spreading of the curve was 7 dB (95% confidence interval 28 dB).     

The influence of δ9-Tetrahydrocannabinol on intraocular pressure in the anaesthetized cat

⁹-Tetrahydrocannabinol (⁹-THC) was injected both intravenously and into the brain stem via the left vertebral artery. Contrary to results obtained with clonidine, neither the fall in intraocular pressure (IOP), nor the arterial hypotension induced by ⁹-THC, were enhanced after the central administration of the drug. For clonidine, a central mechanism underlying the ocular hypotensive effect has recently been proposed. This suggestion is based upon the enhanced fall in IOP after central administration of clonidine. The pontomedullary area is considered to be the main initial target of this drug. Obviously, the IOP-lavering mechanism of ⁹-THC is different from that of clonidine.     

Trabecular aspiration: a new surgical approach to improve trabecular facility in pseudoexfoliation glaucoma

The main reason for elevation of intraocular pressure in pseudoexfoliation glaucoma is due to secondary plugging of the intertrabecular spaces by pigment and fibrillous material. The aim of the present study was to introduce a new surgical concept to clean trabecular meshwork in pseudoexfoliative glaucoma. Trabecularaspiration was performed under the operating microscope prior to extracapsular cataract extraction in half of the chamber angle circumference using a specially designed irrigation-aspiration device. The hand-held instrument has three outlets, one for aspiration (400m wide and 45 horizontally angulated to meet the slope of the meshwork) and two openings (650m) for irrigation to maintain a deep anterior chamber and to keep the iris away from suction. Trabecular debris and pigment was cleared with a suction force of 100–200 mmHg. The effect oftrabecular aspiration was cross-checked by analysing the aspirate. Pigment granules, fibrillous protein and other forms of trabecular debris were identified in the aspirate using light- and scanning electron microscopy. The morphological analysis of the trabecular aspirate clearly indicates the efficacy oftrabecular aspiration for removing pre- and intratrabecular debris. The clinical relevance of this new procedure looks promising, a clinical trial, recently initiated, is warranted.     

Slit lamp ophthalmodynamometry

A short clinical trial of the Dynoptor Slit Lamp Ophthalmodynamometer has shown it to be a practical instrument. A mean O.A.P. of 52.3 mm/hg has been recorded.     

Freeze-fracture replica of the primate lens fibers

Summary Using freeze-fracture techniques, we studied the fine structure of monkey lens fibers, with special reference to intercellular junctions. Gap junctions were frequently observed at the ball- and-socket interdigitations, the tongue- and-groove interdigitations, and between cortical lens fibers, while tight junctions were never apparent.     

Electroretinogram responses and refractive errors in patients with a history of retinopathy of prematurity

Ametropias, particularly myopia, and mild retinal dysfunction are found in eyes with a history of retinopathy of prematurity. The retina is an important controller of refractive development. The aims of this study were to find out whether altered measures of retinal function and ametropias are associated and to consider mechanisms by which the retina might control refractive development. Nine infants and children with a history of stage 1, 2 or 3 retinopathy of prematurity and known courses of refractive development were studied. Spherical equivalents at the time of the electroretinogram ranged from +5.50 to –9.00 diopters. Rod photoresponse characteristics were derived from the a-wave, and postreceptoral components were also analyzed with calculation of the sensitivity and saturated amplitude of the b-wave, the sensitivity of oscillatory wavelet OP₂, and average amplitudes of OP₃ and OP₄. In hyperopic and myopic patients alike, the saturated amplitude and gain of the rod cell response were attenuated. In all patients, b-wave sensitivity was low, but in most there was little effect on saturated b-wave amplitude. In patients with courses toward myopia, the amplitude of OP₄, an OFF signal, is relatively more attenuated than that of OP₃, an ON signal. OP₄ is relatively larger in patients with courses toward hyperopia. The OP results suggest that an imbalance of ON and OFF activity in the retina is associated with development of ametropias in retinopathy of prematurity.Abbreviation ROP retinopathy of prematurity     

Visual field testing with reduced sets of test points

A computerized analysis of visual fields is described. In a second step these results are condensed into a reduced set of test points so constructed that if testing is limited to 6–8 points nearly all defective visual fields would have been spotted with at least one defective point.The reduced set is suggested as the basis in programmes for spotting glaucoma cases at an early stage.Using a reduced set involves the testing of few points several times in a session rather than spending very few trials on a great number of points. This is a new approach which merits further investigation.     

Trachoma through history

History of ophthalmia is as old as history itself; no race or community is immune to it. There were times when blinding trachoma took a form of disastrous epidemics. The historical and recent literature are reviewed in this paper.     

The neural crest origin of uveal melanomas

On the basis of two cases the relation between neurogenic tumours (neurinomas, neurilemmomas, Schwannomas, neurofibromas) and malignant melanomas of the uvea is discussed with emphasis on the close association of both groups of neoplasms with the ciliary nerves. The great histopathological diversity between different cases of melanoma as well as within individual cases is also pointed out. On histological and cytological criteria it may be difficult to differentiate between the neurogenic tumours and the highly differentiated, spindle cell variants of the melanomas. Since all these tumours are derived from the neural crest, they might be grouped under one common heading. It is postulated that neurogenic tumours have been overdiagnosed to the disadvantage of the highly differentiated spindle cell melanomas.     

A perimetric nerve fiber bundle map

The so-called nerve fiber bundle defects in the visual field are considered as being the fuctional equivalent of retinal nerve fiber bundle damage. This study examines the course and the position of scotoma borders in 159 visual fields with complete nerve fiber bundle defects using high resolution test point patterns. The scotoma border lines were averaged geometrically. The result is presented in the form of mean vectors.This functional map of nerve fiber lines shows a close correspondence to the anatomical course of the retinal nerve fibers. To make the result suitable for topographical analysis of visual fields, 21 areas (Perimetric Nerve Fiber Bundles) are defined. Certain arbitrary assumptions were neccessary because data were to scanty in some nasal regions. Also, the lines had to be fitted into a rectangular grid to be transferable to standard perimetric patterns.Topographical analysis on the basis of these areas may be useful for the evaluation of visual fields, particularly those of glaucoma.     

Monitoring demyelination in multiple sclerosis with multi-flash campimetry

Multi-flash campimetry is a computer-implemented psychophysical technique that allows a rapid and extensive assessment of visual flicker sensitivity. Multi-flash field maps generated from the data typically reveal the presence of islands of degraded temporal resolution in multiple sclerosis (MS) patients, but not in normal control observers. These distinct islands presumably reflect the influence of demyelination as well as a variety of other possible transient factors, such as edema and inflammation of the optic nerve. The question addressed in the present study concerned a means of distinguishing among such influences.The strategy employed was to test MS patients more than once over a period of several months. Under the assumption that there is little or no significant remyelination in the central nervous system, it was argued that islands that remain present over time should be those that principally reflect demyelination. Transient changes that appear in the fields of MS patients probably reflect the influence of other mediating factors. Examples of multi-flash field maps are presented to illustrate this point and to serve as an initial assessment of the reliability of the technique. It is concluded that multi-flash campimetry may prove to be an effective aid in documenting the degree of progressive visual involvement in MS, and provide a means of monitoring the clinical course of demyelination in the visual system.     

Extrapolating global visual field indices from local parameters in the nasal region

The local mean and the average difference of four pairs of test locations within the 26° visual field, situated above and below the horizontal nasal meridian, were used to predict the global field indices MD and CLV of the Gl glaucoma program. Out of 539 examinations (194 eyes suspected of having glaucoma), the local indices NDIFF (describing asymmetrical behavior around the nasal horizontal meridian), ND0 (the mean defect in the nasal region), and the global indices MD and CLV were calculated. Seven hundred fifty-five examinations (446 normal eyes) served as a control group. First and second examinations of 146 glaucoma suspect eyes were used to calculate the retest reliability scores for the indices in question. When analyzing the glaucoma suspects, the local index NDIFF, together with the local mean defect, ND0, yielded highly reliable estimates of the global indices MD and CLV, with a retest correlation r = 0.86 for NDIFF, and r = 0.96 for ND0. The covariance of NDIFF with CLV was r = 0.67, while the co-variance of MD with ND0 was r = 0.95.The ranges of the local indices ND0 and NDIFF were each classified into normal range and range of suspected pathology, in analogy to the normal and pathological ranges of the global field indices. Equivalence of the local indices with the corresponding ranges of MD and CLV was investigated and the results are shown. The establishment of local indices may prove to be a powerful tool in early detection of glaucomatous damage.     

Immunodiagnosis of ocular chlamydial infection

The diagnostic roles of enzyme immunoassay and indirect immunofluorescence tests were studied in 99 patients with various grades of active trachoma and in 72 patients with inactive trachoma. Normal invididuals and patients with non-specific chronic conjunctivitis were used as a control group. Chlamydial antigens were detected in the conjunctival swabs from a large proportion of patients with severe or moderate trachoma. Cases with antigen-negative but clinically severe trachoma showed presence of specific IgG in the blood, thus indicating that serological tests may complement the ELISA test for the detection of chlamydia in infected tissues. The nature of cellular reaction in the conjunctiva seems to be related to the severity of trachoma and presence of the infective organism. Antigen-negative trachoma thus represents either an error of diagnosis or limited sensitivity of currently available immunologic techniques, or a predominantly hypersensitivity state triggered by transient tissue parasitism. Recombinant DNA technology and chronobiologic study of infiltrating lymphocytes are likely to provide some insight in such cases.     

Pterygium excision with or without postoperative irradiation,a double-blind study

A double-blind study (covering 40 months) of 40 eyes with a pterygium which had not previously been operated on, was carried out to study the effect of postoperative irradiation. Nineteen eyes were treated by the bare sclera operation technique only and in 13 cases (68%) a recurrence occurred within 4 months. In 18 eyes from the group of patients treated with Sr 90 irradiation on the 1st, 7th and 14th postoperative day (maximum 3×1000 rad) no recurrences were seen.Patients with a recurrent pterygium and diplopia, symblepharon, visual disturbances (growth over the pupil or severe astigmatism) or many previous operations, were treated by lamellar keratoplasty (Dake, 1980). The recurrences without these complications were treated with success by the bare sclera technique and postoperative irradiation.Complications did not occur in any of the series.     

Results of a filtering procedure in low tension glaucoma

Twenty-six eyes of twenty patients with established low tension glaucoma, who had either a double flap Scheie filtering operation or a trabeculectomy, were followed over a period ranging from one to ten years, with a median of three years. These 26 eyes include two second eyes that served as a contralateral control eye until the visual field deteriorated. All 26 eyes showed progression of visual field defects preoperatively, while postoperatively only 2 eyes showed further progression. Of the 16 nonoperated contralateral eyes, 7 showed progression of visual field defects over the same follow-up period. Two of these 7 eyes had to be operated during the study-period. The difference in progression between the operated and the non-operated eyes was significant (P<0.01). The diltering procedure provided a reduction in IOP of 20% or more in 21 of 26 eyes. There was a significant difference in the mean intraocular pressure (IOP) between the operated and the non-operated contralateral eye of 6.8 mmHg (37%) at one year postoperatively. The diurnal variation decreased highly significantly from 4.3 to 2.1 mmHg (P<0.001). It is concluded that filtering surgery in low tension glaucoma may result not only in a significant lowering of IOP, but is also effective in slowing further deterioration of the visual fields.Supported in part by a grant from De Rotterdamse Vereniging Blindenbelangen.Presented in part by N. de Jong at the 180th Meeting of the Netherlands Ophthalmological Society, Apeldoorn, March 1986.