Functional characteristics of blue-on-yellow perimetric thresholds in glaucoma.

PURPOSE: Blue-on-yellow (B-on-Y) perimetry assesses the S-cone visual field under yellow adaptation. Glaucomatous field defects have been shown to appear earlier and to be larger in B-on-Y perimetry than in standard perimetry. An upper limit to the use of B-on-Y perimetry is set by the separation of the S-cones from the M- and L-cones. But, because the S-cones may also input to the luminance channel, the actual separation of the color and luminance channels is unknown. Here, the relative sensitivities of the color and luminance channels under B-on-Y test conditions are measured. METHODS: In 15 eyes with early glaucoma, 19 risk eyes, and 10 normal eyes, B-on-Y thresholds were measured from 0 degrees to 20 degrees eccentric and were compared to pure chromatic (B-in-Y) and achromatic (Y-on-Y) thresholds, obtained under identical yellow adaptation. RESULTS: In normals, B-on-Y thresholds were found to coincide with B-in-Y thresholds; Y-on-Y values were 0.5 log (at 20 degrees) to 0.9 log (at 0 degrees) higher. In the pathologic groups, the differences between B-in-Y and Y-on-Y thresholds were smaller. Pathologic threshold elevation is on average 1.8 times larger for chromatic than for achromatic stimuli. In some cases, the luminance channel takes over detection of the B-on-Y stimulus. CONCLUSIONS: In normals, the B-on-Y stimulus is mediated by the color channel. Takeover of detection by the luminance channel might impose limits on following color defects with B-on-Y perimetry. This takeover may occur before the S-cones become less sensitive than the M- and L-cones and might indicate S-cone input to the luminance channel.

The additive intraocular pressure-lowering effect of latanoprost in combined therapy with other ocular hypotensive agents.

Latanoprost, a prostaglandin F2 alpha analogue prodrug, has been shown to be an effective ocular hypotensive agent when used alone on ocular hypertensive or open angle glaucoma patients. In various studies, the ocular hypotensive effects of latanoprost have also been evaluated when used in addition to, or in combination with, other ocular hypotensive agents. Latanoprost produces an additional reduction of intraocular pressure (IOP) when used in combination with timolol, pilocarpine, acetazolamide and dipivefrin. These represent four different classes of glaucoma drugs-beta-adrenergic antagonists, cholinergic agonists, carbonic anhydrase inhibitors, and adrenergic agonists-all of which reduce the IOP by different mechanisms (reduction of aqueous humor production, increased outflow facility, or by a mixed effect on aqueous humor dynamics). All the available evidence shows that latanoprost produces a clinically significant additive ocular hypotensive effect when used in combination with any currently available ocular hypotensive agent.

Fluorescein angiographic evaluation of the effect of latanoprost treatment on blood-retinal barrier integrity: a review of studies conducted on pseudophakic glaucoma patients and on phakic and aphakic monkeys.

Endogenous prostaglandins (PGs) have been claimed to play a role in the development of cystoid macular edema (CME). Two fluorescein angiographic studies evaluating the effect of latanoprost, a new ocular hypotensive PG analogue, on blood-retinal barrier integrity are, therefore, reviewed here. In the first study, six of eight unilaterally aphakic cynomolgus monkeys were treated bilaterally once daily for six months with 0.035% latanoprost (seven times the clinically used oculohypotensive concentration). Two of the animals served as controls. Fluorescein angiography of the fundus after one, three and six months of treatment revealed no leakage of fluorescein in any of the 16 eyes. In another study, pseudophakic eyes of 16 glaucoma patients who received twice-daily treatment with 0.006% latanoprost for four weeks were compared to eight patients treated with placebo. Biomicroscopic examination did not reveal any signs of CME and only one placebo-treated eye revealed a slight perifoveal leakage of fluorescein. These studies suggest that topically-applied latanoprost does not have a fluorescein angiographically detectable direct effect on the integrity of the blood-retinal barrier system in phakic or aphakic monkey eyes or in pseudophakic human eyes. This does not rule out the occurrence of CME in eyes more susceptible to CME, due to vitreous loss, posterior capsulotomy, or other postoperative situations. Especially in those eyes a study with latanoprost is proposed. Since, fluorescein angiography is a rather crude method of detecting abnormalities of the blood-retinal barriers, vitreous fluorometry in addition is suggested.

Reduced intraocular pressure and increased ocular perfusion pressure in normal tension glaucoma: a review of short-term studies with three dose regimens of latanoprost treatment.

Currently used ocular hypotensive agents do not effectively lower intraocular pressure (IOP) in some normal-tension glaucoma (NTG) patients. The prostaglandin F2 alpha analogue, latanoprost, has been shown to reduce IOP in normal subjects and ocular hypertensive glaucoma patients by increasing uveoscleral outflow. This mechanism is expected to be particularly effective in the lower IOP range that is typical of NTG. To date, three dose regimens of latanoprost have been shown to reduce IOP significantly in NTG. The IOP reductions of 14.2% and 15% obtained with twice-daily application of 0.0015% and 0.006% latanoprost, respectively, were comparable to the modest IOP reduction that has been reported for other glaucoma drugs in NTG. In contrast, once-daily application of 0.005% latanoprost resulted in a 21.4% IOP reduction. In another study that included 24-hour monitoring of systemic blood pressure and heart rate in NTG patients, the ocular perfusion pressure was found to improve more on once-daily 0.005% latanoprost than on twice-daily treatment with 0.5% timolol. Thus, once-daily 0.005% latanoprost appears to be a more effective and more convenient ocular hypotensive agent for treating NTG than currently used glaucoma drugs. However, long-term studies will ultimately be needed to establish the efficacy of this new drug to delay or prevent the progression of visual field loss in normal tension glaucoma.

A comparison of retinal and choroidal hemodynamics in patients with primary open-angle glaucoma and normal-pressure glaucoma.

PURPOSE: To quantify, compare, and assess differences between retinal and choroidal hemodynamics in normal control subjects and patients with ocular hypertension, primary open-angle glaucoma, and normal-pressure glaucoma. METHODS: Video fluorescein angiograms were made in 20 normal subjects, 11 patients with ocular hypertension, 45 patients with primary open-angle glaucoma, and 43 patients with normal-pressure glaucoma. Choroidal dye build-up curves were analyzed using an exponential model. The model time constant tau reflected the local blood refreshment time, the time needed to replace the blood volume in a tissue volume. Retinal arteriovenous passage time was estimated from the time lapse between retinal arterial and venous dye curves. RESULTS: The retinal arteriovenous passage time was longer in patients with primary open-angle glaucoma compared with normal subjects and patients with normal-pressure glaucoma; the average arteriovenous passage times (+/-SEM) in normal subjects and in patients with ocular hypertension, primary open-angle glaucoma, and normal-pressure glaucoma were, respectively, 2.44 +/- 0.19, 2.90 +/- 0.37, 3.02 +/- 0.17, and 2.55 +/- 0.15 seconds. Choroidal tau was longest in the normal-pressure glaucoma group but not as long in the primary open-angle glaucoma group; tau values in normal subjects and patients with ocular hypertension, primary open-angle glaucoma, and normal-pressure glaucoma were, respectively, 4.6 +/- 0.29, 5.6 +/- 0.69, 6.2 +/- 0.39, and 7.1 +/- 0.33 seconds. CONCLUSIONS: Whereas choroidal circulation is especially slower in patients with normal-pressure glaucoma, retinal circulation is delayed in patients with primary open-angle glaucoma. The choroidal and retinal vascular systems behave differently in primary open-angle and normal-pressure glaucoma, which may be important in the management of glaucoma.

Use of the Megasoft Bandage Lens for treatment of complications after trabeculectomy.

Shallow anterior chambers and leaking filtration blebs are possible complications after trabeculectomy that can be treated with therapeutic contact lenses. In most cases, however, treatment fails because these lenses are not large enough to cover the filtering bleb. We evaluated the use of a newly developed large diameter (20.5 mm) therapeutic soft contact lens. Five patients with shallow anterior chambers and ten patients with leaking filtering blebs after trabeculectomy were fitted with this new extended-wear contact lens. All patients with shallow anterior chambers developed deep chambers after a mean treatment period of five days. Of the ten patients with leaking filtering blebs, in eight (80%) the leak closed after a mean treatment period of 2.2 months. The contact lens used was comfortable and complications occurred in only one eye. This new therapeutic device is an improvement in the treatment of complications after trabeculectomy.

Treatment of hypotonous maculopathy after trabeculectomy with mitomycin C.

We treated 34 eyes of 32 patients who developed a hypotonous maculopathy after a trabeculectomy with mitomycin C with various treatment strategies. Placement of a Megasoft Bandage Contact Lens in 24 eyes did not result in a notable increase in intraocular pressure or visual acuity. Intrableb injection of autologous blood in 22 eyes resulted in a mean +/- standard deviation (S.D.) increase in intraocular pressure from 4.3 +/- 1.8 mm Hg before injection to 8.6 +/- 4.6 mm Hg after injection. Mean logMAR visual acuity improved from 0.71 +/- 0.40 to 0.32 +/- 0.25. After a surgical revision of 16 eyes, intraocular pressure increased from 4.1 +/- 1.9 mm Hg to 11.3 +/- 4.0 mm Hg, and logMAR visual acuity improved from 0.61 +/- 0.30 to 0.22 +/- 0.24. At the last follow-up examination (12.2 +/- 5.1 months after the trabeculectomy), 31 eyes (91.2%) had an intraocular pressure greater than 6 mm Hg. Hypotonous maculopathy after trabeculectomy with mitomycin C can be treated successfully by autologous blood injection and surgical revision of the filtration site.

Retinal nerve fiber layer assessment by scanning laser polarimetry and standardized photography.

PURPOSE: To determine whether, in a clinical setting, scanning laser polarimetry and retinal nerve fiber layer photography provide equivalent information on the retinal nerve fiber layer. METHODS: We prospectively studied 60 patients with glaucoma or ocular hypertension and 24 healthy subjects. With scanning laser polarimetry, an estimate of the cross section of the retinal nerve fiber layer was obtained. By using a photographic reference set, we quantified photographs of the retinal nerve fiber layer. Visual fields were used to relate the results of both methods to functional damage. RESULTS: The scanning laser polarimetry measurements yielded reproducible cross-section values (coefficient of variation, 6.6%). Comparison of cross-section values and photograph scores gave Pearson correlation coefficients smaller than r = .4 (P < .01), improving to a maximum of r = .53 after compensation for offset. When cross-section values were compared to the mean deviation of the visual field, the Spearman correlation coefficients varied from an r of -.34 to -.53 (P < .01). Correction for offset resulted in an r of -.54 to -.65. When photograph scores and mean deviation of the visual field were compared, the Spearman correlation coefficients varied from an r of -.65 to -.71 (P < .01). CONCLUSIONS: Because r was maximal at .53, the information on the retinal nerve fiber layer obtained with scanning laser polarimetry and photography seems not equivalent. This result could not have been because of lack of reproducibility. Although the results suggested possible offset in scanning laser polarimetry, other methodologic differences must be considered to explain the differences between the two techniques.

Histopathologic effects of mitomycin C after trabeculectomy in human glaucomatous eyes with persistent hypotony.

We evaluated the histopathologic findings in seven patients who underwent surgical revision of the filtration site after trabeculectomy with mitomycin C because of persistent hypotonous maculopathy. Light microscopic examination of subconjunctival tissue and sclera demonstrated hypocellularity of fibroblasts and disruption of the normal architecture. Tissue fragments at the margin of the bleb wall demonstrated scarring and contained multiple fibroblasts. Additionally, we investigated the histopathologic changes in an eye obtained from a patient who died one week after a trabeculectomy with mitomycin C. Transmission electron microscopy showed myelin figures, increased melanolipofuscin granules, vacuolated cytoplasm, and disrupted mitochondria of the ciliary body epithelium underlying the site of mitomycin C application. On the basis of these findings, both overfiltration because of tissue disorganization of the filtering bleb and aqueous hyposecretion because of ciliary body toxicity might be involved in the causes of persistent hypotony after mitomycin C trabeculectomy.

Rapid deterioration of visual fields during bromocriptine-induced pregnancy in a patient with a pituitary adenoma.

A 28-year-old woman with an amenorrhoea-galactorrhoea syndrome was suspected of a microadenoma of the pituitary. She was treated with bromocriptine. In the subsequent pregnancy she developed rapid deterioration of the visual fields (ODS). A large temporal defect in the right eye and a moderate temporal defect in the left eye appeared in the 28th week of pregnancy, threatening the visual acuity of both eyes. Other examinations showed no evident lesion of the sellar region. An adenoma of the pituitary was removed, and the visual fields returned to normal after operation.

Additive effect of latanoprost, a prostaglandin F2 alpha analogue, and timolol in patients with elevated intraocular pressure.

A randomised observer masked clinical study was conducted to assess the additive effect of latanoprost (13,14-dihydro-17-phenyl-18,19,20-trinorprostaglandin F2 alpha-isopropylester) to timolol maleate in patients with elevated intraocular pressure (IOP). Patients were randomly assigned to two treatment groups. One group (n = 10) received timolol, the other group (n = 9) received latanoprost twice daily for 1 week. After 1 week all patients received both timolol and latanoprost. Eyes treated with timolol (mean diurnal IOP (SD) day 0, 24.2 (2.8) mm Hg) and latanoprost (mean diurnal IOP day 0, 28.5 (5.6) mm Hg) showed an IOP reduction of 5.9 (2.3) mm Hg (24%) and 8.9 (2.5) mm Hg (31%), respectively after the first week. Adding latanoprost to the eyes treated with timolol as well as timolol to the eyes receiving latanoprost gave a further reduction of 2.6 (1.1) mm Hg (13%) and 2.6 (2.2) mm Hg (14%), respectively. Only mild transient hyperaemia was observed in patients receiving latanoprost. The results indicate that latanoprost and timolol can be combined successfully and that complete or almost complete additivity is reached even at pressure levels below 20 mm Hg.

Choroidal haemodynamics in glaucoma.

AIM: Quantification of haemodynamics of the peripapillary choroid in and the assessment of possible differences between normal subjects (N), ocular hypertensive (OHT), primary open angle (POAG), and normal pressure glaucoma (NPG) patients. METHODS: Video fluorescein angiograms (Rodenstock SLO 101) were made in 22 N subjects, 12 OHT, 48 POAG, and 46 NPG patients. The angiographically derived dye build up curves were described by means of an exponential model. One of the model parameters is the time constant tau theoretically reflecting local blood refreshment time; the blood refreshment time tau is the time needed to replace the blood volume in the choriocapillaris, inversely proportional to the local choroidal blood flow. Other variables are maximal fluorescence (Fdt) and time of first fluorescence (t0). Mean variable values were calculated for disc area and circular areas around the disc. RESULTS: Fdt of the disc was significantly lower in the POAG and NPG patients. There was no statistical difference in t0 between the study groups. The choroidal blood refreshment time was significantly longer in NPG patients and to a lesser extent in the POAG patients compared with the normal controls. The slowest choroidal blood refreshment can be found in the NPG group. The median choroidal blood refreshment times (25th-75th percentile) in the controls, OHT, POAG, and NPG patients were 4.1 (3.7-4.5), 4.4 (3.7-6.4), 5.8 (4.3-6.8), and 7.1 (5.5-9.3) seconds respectively. CONCLUSIONS: With the help of parametrisation of dye curves, using a one compartmental model, choroidal haemodynamics can be quantified. The blood refreshment time of the peripapillary choriocapillaris was found to be significantly prolonged especially in NPG patients; this may indicate slower choroidal haemodynamics in NPG patients.

Blood and plasma viscosity measurements in patients with glaucoma.

Blood viscosity at 10 shear rates, plasma viscosity, packed cell volume, plasma fibrinogen, serum alpha 2-macroglobulin, and serum proteins were measured in 83 patients with low-tension glaucoma (LTG) and 23 patients with 'high-tension glaucoma' (HTG: at least one IOP reading above 40 mmHg) and compared with those in 50 controls. Blood and plasma viscosity values and packed cell volume were significantly higher in the LTG group than those in controls. The HTG and the LTG groups differed only in plasma viscosity, but smoking and drinking habits in the HTG patients were greatly different from those in LTG patients and controls, thus preventing interpretation of data in the HTG group. Within the LTG group viscosity values were highest in a subgroup designated earlier by us as focal ischaemic LTG, whereas another subgroup, senile sclerotic LTG, did not show significant differences compared with controls. These findings may indicate a factor in the pathogenesis of visual field defects and disc cupping in some patients with LTG.

Results of cataract surgery and implantation of a compressible disc lens in patients with glaucoma.

We studied the efficacy and postoperative behavior of a compressible disc posterior chamber intraocular lens in 40 eyes of 33 glaucoma patients. They had a mean follow-up of 12.8 months. Postoperatively, 38 eyes (95%) had a best corrected visual acuity of 20/40 or better. Minor decentration occurred in one case. Early posterior capsule fibrosis (40%) was 50% less than in earlier reports on the rigid Galand disc IOL. Posterior synechias were present in 35% of eyes. Postoperative complications such as pupil capture (0%) and significant posterior capsule opacification (12.5%) were minimized by using this IOL. Closed-loop circular lenses are an attractive alternative to open-loop-supported IOLs in patients with glaucoma.

Early posterior capsular opacification after intercapsular cataract extraction and rigid Galand disc intraocular lens implantation.

From retrospective studies of implantation of the rigid Galand disc intraocular lens (IOL) and the Sinskey style J-loop IOL, we found that posterior capsular opacification was more common and developed faster in eyes implanted with a Galand disc IOL than in eyes implanted with a Sinskey style J-loop IOL. We investigated this further in a clinical study of 20 patients implanted with a Galand disc IOL. We found a specific type of posterior capsular haze, resembling a "moon landscape," in 10 (50%) of the 16 eyes (80%) with capsular fibrosis.

Lens extraction for uncontrolled angle-closure glaucoma: long-term follow-up.

PURPOSE: To evaluate the long-term effects of extraction of incipient cataracts or clear lenses on glaucoma control in patients with subacute or chronic angle-closure glaucoma. SETTING: Department of Ophthalmology, University of Amsterdam, The Netherlands. METHODS: This retrospective analysis comprised 22 extracapsular lens extractions with implantation of a posterior chamber intraocular lens in 18 patients with chronic or subacute angle-closure glaucoma (Group 1). The effect of glaucoma control was evaluated using visual field examination, diurnal intraocular pressure (IOP) curves, gonioscopic appearance, and number of antiglaucoma medications. The results were compared with those in 25 eyes of 19 patients with chronic angle-closure glaucoma in whom a filtering procedure was performed (Group 2). RESULTS: Glaucoma control was achieved in 15 eyes (68%) in Group 1 and in 17 eyes (68%) in Group 2. Mean preoperative IOP was 27.9 mm Hg +/- 8.1 (SD) and 29.0 +/- 7.7 mm Hg, respectively. Mean postoperative IOP was 17.1 +/- 2.9 mm Hg (Group 1) and 14.8 +/- 6.6 mm Hg (Group 2) after a mean follow-up of 52.6 and 58.9 months, respectively. Mean number of ocular hypotensive medications preoperatively was 2.3 +/- 0.8 in Group 1 and 2.2 +/- 0.8 in Group 2 and at last follow-up, 1.3 +/- 0.7 and 0.52 +/- 0.8, respectively. Twenty eyes (91%) in Group 1 had the same or better final visual acuity than before surgery. In Group 2, the final visual acuity was unchanged or better in 13 eyes (52%) and worse in 12 eyes (48%); subsequent cataract surgery was performed in 9 (75%) of these 12 eyes. Additional incisional surgery was done or recommended in 6 eyes (27%) in Group 1 and 20 eyes in Group 2 (80%). CONCLUSION: Drainage surgery in patients with angle-closure glaucoma proved to be associated with multiple surgical interventions and deterioration in visual function. The choice of first a cataract procedure with the option of a future trabeculectomy may be a more attractive approach in patients with subacute or chronic angle-closure glaucoma than trabeculectomy followed by an optional cataract procedure.

The effects of 5-fluorouracil and mitomycin C on the corneal endothelium.

5-Fluorouracil (5-FU) and Mitomycin C (MMC) are used as adjunct chemotherapy during glaucoma filtering surgery to suppress conjunctival fibroblast proliferation. Since part of these agents may gain access to the anterior chamber and cause cytotoxicity to the corneal endothelium we set up an in vitro system to establish a dose-response effect. Cytotoxicity of MMC and 5-FU was quantified using Mosmann's colorimetric assay in a bovine endothelial cell culture system. In this assay the respiratory activity of the cells is used as a marker for cell viability. After incubation for 5 minutes the 3.0 mg/ml concentration of MMC showed endothelial cytotoxicity, whereas no endothelial toxicity of 5-FU was noted in concentrations up to 50 mg/ml. After incubation for 30 minutes endothelial cytotoxicity was demonstrated for 50 mg/ml of 5-FU and 1 mg/ml of MMC. After an exposure-time of 60 minutes the toxicity level remained 50 mg/ml for 5-FU but decreased to 0.5 mg/ml for MMC. We conclude that with respect to the clinically used concentrations and methods of application of 5-FU and MMC in vivo endothelial toxicity is not to be expected. However, in cases of accidental access of MMC to the anterior eye chamber and following a reduction of aqueous turnover rate the safety of MMC is unwarranted.

Assessment of the nasopharyngeal airway. A rhinomanometric and radiographic study in children with adenoids.

An assessment of the nasopharyngeal airway in 24 children referred to hospital for adenoidectomy was based on symptoms, radiography and rhinomanometry. The only symptom that was significantly correlated to a small size of the nasopharyngeal airway was Snoring. By radiography, measurement of the airway as well as of the depth of soft tissue of the posterior wall was found well correlated to nasal respiratory resistance which was measured by a new technique. By this, rhinomanometry could be performed in all children down to the age of 5 years. Both radiography and rhinomanometry give valuable parameters for the indication of adenoidectomy.

Rhinomanometric recording in children.

The present paper describes the development of a method for rhinomanometric assessment of nasal respiratory resistance in children, based on a commercially available equipment, the Mercury Nasal Resistance Meter, NR 1. The instrument was modified to improve performance, and a special technique was developed for individual lining of the nose mask. The posterior rhinomanometric tehnique was further modified by fitting the oral tubing with a collar, and by the use of a bio-feedback procedure based on oscilloscope display of the flow-pressure diagram. It could then be used in all subjects, a considerable improvement over previous methods. The error of the method was analysed in a sample of 17 children aged 8-12 examined at two occasions. There was no systematic error. For the posterior method the method error within a session was about 0.2 cm H2O/l/sec at a flow rate of 0.2 l/sec.

[Neuroborreliosis--not only Bannwarth's syndrome]. / Neuroborreliose--ikke kun Bannwarth's syndrom.

Two patients with neuroborreliosis are reported. They had Bannwarth's syndrome combined with encephalitis and myelitis respectively. Both patients recovered following high-dose penicillin treatment. Neuroborreliosis may be complicated with CNS involvement although this may be infrequent. It is important to diagnose neuroborreliosis because of the striking effect of penicillin treatment.