Ethnic variability of the vasculature of the optic disc in normal and in glaucomatous eyes.

PURPOSE: Although disc pallor is associated with glaucoma, the structural macro-anatomy of the disc vasculature has received little attention, and possible ethnic differences have not been considered. Accordingly we studied the distribution of blood vessels crossing the rim of the optic disc. METHODS: Thirty normal controls, and 50 glaucomatous cases with a unilaterally impaired visual field were studied. The sample populations included white Caucasian, and African and Afro/Caribbean volunteers. A b/w photographic method of imaging the blood vessels crossing the rim of the optic disc was used, the illuminant being green. The prints used in the analysis had been masked during their exposure to enhance contrast. The numbers of vessels, grouped into large (approximately 60nm), medium (approximately 30nm), and small (approximately 10nm) lumina, were counted, the disc images being divided radially into eight equal sectors. RESULTS: While the large vessels crossed the rim mainly along the vertical, the small ones did so mainly in the horizontal. The distribution of the medium vessels was unpolarized but their crossings predominated on the nasal side. The vessel patterns differed significantly between the two ethnic groups as regards both number and distribution along the rim of the disc, the smaller vessels being more numerous in Caucasian eyes (p approximately 0.02). Rim crossings by vessels were smaller in glaucomatous eyes in both ethnic groups. In normal eyes there was a statistically significant age-related decline in the number of small vessels after the age of 20 years. CONCLUSIONS: There exists a statistically significant inverse relation between the number of capillaries crossing the disc rim and the vertical cup/disc ratio. Caucasian rims show the larger number of capillaries crossing.

Ethnic variability of the vasculature of the optic disc in normal and glaucomatous eyes.

PURPOSE: Although disc pallor is associated with glaucoma, the structural macro-anatomy of the disc vasculature has received little attention, and possible ethnic differences have not been considered. Accordingly we studied the distribution of blood vessels crossing the rim of the optic disc. METHODS: Thirty normal controls, and 50 glaucomatous cases with a unilaterally impaired visual field were studied. The sample populations included white Caucasian, and African and Afro/Caribbean volunteers. A b/w photographic method of imaging the blood vessels crossing the rim of the optic disc was used, the illuminant being green. The prints used in the analysis had been masked during their exposure to enhance contrast. The numbers of vessels, grouped into large (~60nm), medium (~30nm), and small (~10nm) lumina, were counted, the disc images being divided radially into eight equal sectors. RESULTS: While the large vessels crossed the rim mainly along the vertical, the small ones did so mainly in the horizontal. The distribution of the medium vessels was unpolarized but their crossings predominated on the nasal side. The vessel patterns differed significantly between the two ethnic groups as regards both number and distribution along the rim of the disc, the smaller vessels being more numerous in Caucasian eyes (p~0.02). Rim crossings by vessels were smaller in glaucomatous eyes in both ethnic groups. In normal eyes there was a statistically significant age-related decline in the number of small vessels after the age of 20 years. CONCLUSIONS: There exists a statistically significant inverse relation between the number of capillaries crossing the disc rim and the vertical cup/disc ratio. Caucasian rims show the larger number of capillaries crossing. (Eur J Ophthalmol 2004; 14: #-507).

Clinical dose-regimen studies with latanoprost, a new ocular hypotensive PGF2 alpha analogue.

This review summarizes recent short-term clinical studies evaluating the ocular hypotensive efficacy of different dose-regimens of latanoprost. When tested in ocular hypertensive and glaucoma patients concomitantly treated with timolol, 0.006% latanoprost given only in the evening, was found to be more effective than the same concentration given in the morning and evening. In patients with open angle, pseudoexfoliation and normal tension glaucoma not receiving other treatment, once-daily 0.005% latanoprost monotherapy was more effective than twice-daily 0.0015% latanoprost treatment. No significant differences were found in conjunctival hyperemia, sensory irritation or blood-aqueous barrier permeability between these two treatment regimens. Although the ocular hypotensive efficacy of once-daily application of the lower concentration (0.0015%) latanoprost was not investigated, we would conclude, based on the studies reviewed here, that at a concentration of 0.005%, once-a-day dosing of latanoprost is highly effective in significantly reducing intraocular pressure, causing only minimal, clinically acceptable short-term ocular side effects.

Long-term effects of glaucoma therapy with 4% pilocarpine gel on corneal clarity and endothelial cell density.

Corneal thickness measurements and endothelial cell counts were carried out in 34 patients undergoing treatment for glaucoma with 4% pilocarpine gel between 18 to 78 months after initiation of therapy. The corneal thickness and endothelial cell population were found to be within normal limits in all cases except two, one patient with increased corneal thickness who had recently undergone cataract and glaucoma filtering surgery and another patient with decreased cell count who had an old endothelial scar sustained prior to pilocarpine gel therapy. There was a very close correlation for both of these parameters noticed in patients treated with pilocarpine gel and in age-matched control group of patients with glaucoma. The present study has shown that there are no adverse corneal effects with pilocarpine gel therapy.

Intraocular pressure-reducing effect of PhXA41 in ocular hypertension. Comparison of dose regimens.

PURPOSE: To investigate the intraocular pressure (IOP)-reducing effect and side effects of PhXA41, a new prostaglandin F2 alpha (PGF2 alpha) analog, in ocular hypertension and to compare two different dose regimens of PhXA41. METHODS: This was a 2-week randomized, placebo-controlled, double-masked study. PhXA41 eye drops at a concentration of 0.006% (60 micrograms/ml) were administered either once daily (evening) or twice daily (morning and evening) to patients with bilateral ocular hypertension. Each PhXA41 group consisted of 20 patients and the placebo group consisted of 10. RESULTS: PhXA41, administered once or twice daily, reduced IOP by 8.9 and 7.1 mmHg, respectively, in the two treatment groups at the end of the 2-week treatment period. No clear-cut drift in the IOP reduction was observed during the treatment period, but the maximum response was obtained on day 2 in the group receiving PhXA41 twice daily. Both dose regimens of PhXA41 caused more conjunctival hyperemia than the placebo. At the end of the treatment period, 64% to 74% of the patients receiving PhXA41 exhibited no or barely detectable hyperemia. The corresponding figure in the placebo group was 90%. PhXA41 was well tolerated and only one patient dropped out of the study. CONCLUSIONS: PhXA41 reduced IOP by 28% to 36% in patients with ocular hypertension with only mild side effects. Dosing once daily was at least as effective as twice daily. PhXA41 has the potential of becoming a useful new drug for glaucoma treatment.

Comparison of apraclonidine and timolol in chronic open-angle glaucoma. A three-month study.

PURPOSE: To compare the safety and efficacy of apraclonidine ophthalmic solution 0.25% and 0.5% (both given 3 times daily) to timolol maleate (0.5%) given twice daily, in primary open-angle glaucoma or ocular hypertension. METHODS: This study was a 90-day prospective, multicenter, double-masked, randomized, parallel group trial. Intraocular pressure (IOP) measurements were made between 8:00 and 10:00 AM before the morning dose (i.e., up to 12 hours after the evening dose of glaucoma medication) and at 4:00 PM (i.e., 8 hours after the morning dose of glaucoma medication). Patients with off-therapy IOP of greater than 22 mmHg and less than 35 mmHg were entered into the study and were assessed 14, 30, and 90 days after treatment. RESULTS: Sixty-nine patients were enrolled; there were no significant demographic differences among the three study groups. All three treatments significantly reduced IOP over 90 days (P < 0.011). For apraclonidine 0.5%, IOP reductions from 25.8 +/- 3.2 mmHg (pretreatment) to 20.4 +/- 4.00 mmHg (day 90) were observed; for apraclonidine 0.25%, from 25.7 +/- 3.05 mmHg (pretreatment) to 22.1 +/- 4.24 mmHg (day 90); and for timolol 0.5% from 26.1 +/- 3.79 mmHg to 21.1 +/- 5.91 mmHg (day 90). The 90-day period of therapy was completed by 12 patients treated with apraclonidine 0.5%, 21 patients treated with apraclonidine 0.25%, and 23 patients treated with timolol 0.5%. There were no serious adverse events. Fourteen of 22 patients (0.5% apraclonidine) and 21 of 23 patients (0.25% apraclonidine) tolerated the drug well; ocular allergy developed in the remaining patients treated with apraclonidine, which resolved upon discontinuation. CONCLUSIONS: Apraclonidine effectively lowers IOP associated with open-angle glaucoma or ocular hypertension; these pilot results will need to be confirmed by a larger pivotal study. Long-term therapy for some patients may be inhibited by ocular allergy for which there was a higher incidence to the 0.5% apraclonidine solution than to the 0.25% solution in this study. Apraclonidine may be of value as an additional therapy for open-angle glaucoma in selected patients.

Argon laser trabeculoplasty in narrow angle glaucoma.

A prospective trial of argon laser trabeculoplasty (ALT) in narrow angle glaucoma (NAG) was undertaken. In eyes with NAG the mechanism of the glaucoma could be a combination of pupil block with subsequent irido-trabecular adhesion and trabecular damage with an increase in outflow resistance. To achieve relief of pupil block, eyes were randomly assigned to treatment with short pulsed laser iridotomy (LI) with the YAG or Dye lasers, or surgical peripheral iridectomy (PI). Alternatively, argon laser iridoplasty (IP) was performed to widen the anterior chamber angle sufficiently to permit ALT. Fifty-two eyes were treated and follow-up was from 12 to 22 months. A high rate of failure to control IOP with topical medication and progression of visual field loss occurred in all treatment groups. Iridoplasty followed by ALT was particularly unsuccessful as, in 50 per cent of cases, progressive synechial closure of the anterior chamber angle occurred following treatment. In eyes treated with PI/LI and ALT, the IOP control was improved in 12 per cent, unchanged in 30 per cent and remained uncontrolled in 58 per cent. By 15 months follow-up, a satisfactory outcome (IOP less than 21 mmHg on topical medication, visual field and acuity stable) was obtained in 24 per cent of the 33 eyes treated with PI/LI and ALT. Thirty-one of these eyes showed visual field loss. Of the 10 eyes that did not receive ALT following PI or LI, 90 per cent had a satisfactory outcome. Eight of these eyes showed little or no visual field loss. The authors conclude that iridoplasty followed by ALT is an unsuitable treatment for eyes with NAG. We further conclude that ALT is unlikely to be of benefit in eyes with NAG and visual field loss, even after pupil block has been relieved. Relief of pupil block alone may help eyes with early NAG without visual field loss.

Association between optic disc haemorrhages in glaucoma and abnormal glucose tolerance.

Data concerning the results of glucose tolerance tests and levels of intraocular pressure were analysed for 120 patients with primary open-angle glaucoma, many of whom had been under observation for a period of four to five years. The patients consisted of two groups: in 62 patients a disc haemorrhage had been recorded at some time during the observation period, and in 58 no haemorrhages had been seen. Patients with disc haemorrhages had a higher incidence of abnormal glucose tolerance or frank diabetes and lower intraocular pressures than those without haemorrhages.

The effects of various levels of intraocular pressure on the rabbit's outflow system.

The effects of various levels of intraocular pressure on the morphology of the rabbit outflow system were investigated. In a total of 20 rabbits, intraocular pressure was maintained at various levels between 0-50 mmHg in the experimental eye and at 20 mmHg in the control eye for 1 hr. Flow rates into the eyes were measured by following the movement of a miniscus through a calibrated capillary tube. Progressive increase in pressure lead to distension and enlargement of the ciliary cleft. The meshwork tissues stretched and distended, and the vessels of the angular aqueous plexus had pressure-sensitive giant vacuoles of their endothelium. These vessels were prone to closure at pressures of 30 mmHg and greater. Difficulties associated with quantitation of giant vacuoles in this species were discussed.

Corneal endothelial changes following short pulsed laser iridotomy and surgical iridectomy.

Pre- and post-operative endothelial specular photo-microscopy was performed on 46 eyes of 29 patients who had been randomly assigned to iridotomy with the Nd:YAG or the dye laser, or to surgical peripheral iridectomy for the relief of pupil block glaucoma. Localised damage to the endothelium was observed in two eyes following Nd:YAG laser iridotomy and in one eye following dye laser iridotomy. No endothelial changes were recognised after surgical peripheral iridectomy. Central corneal endothelial cell densities remained unchanged following all procedures.

The effects of timolol on the active transport across the ciliary epithelium.

The mean transepithelial potential was +4.04 mV (cameral side positive to stroma). The results (Fig. 1) show that the short-circuit current was significantly reduced by timolol at 10(-4) and 10(-2) M (p less than 0.01). Since the short-circuit current across the isolated ciliary epithelium is a measure of active sodium transport in the direction stroma----posterior chamber there is an appreciable fall in Na +/- transport across the ciliary epithelium at a timolol concentration of 10(-4) M. On current values of aqueous humour secretion there would be a corresponding fall in aqueous production. For comparison it is worth recalling that the concentration of timolol in 0.5 per cent eye drops is slightly over 10(-2) M. Exposure of the tissue to timolol, a beta blocker does not seem to affect the subsequent response of the system to isoprenaline, a beta stimulant. A significant stimulation of short circuit current in the dose-range of 10(-4) to 10(-3) M with isoprenaline in a similar preparation was reported by Cole and Nagasubramanian and increase of short-circuit current and/or sodium transport in amphibian epithelia have been reported for catecholamines, and this effect may possibly be due to a decrease of the resistance to ions actively transported by the 'sodium pump' mechanism brought about via cyclic-AMP mediating the action at a cellular level. It appears that timolol has a direct effect on the active transport per se and by reducing the active ion influx can cause a reduction in the volume of aqueous production.

Addition of pindolol to routine medical therapy: a clinical trial.

A double-blind study of pindolol eye drops 0.5% was carried out on 24 patients with primary open-angle glaucoma. Pressures were taken once weekly during three 3-week periods. In one of the periods placebo was given in both eyes, during another pindolol was given in one eye, and during another it was given in the other eye. A drop in pressure averaging 2.79% was found in eyes receiving pindolol compared with the period when they were receiving saline. Substantial placebo effects were found when in-trial pressures were compared with pretrial, but the placebo effects were avoided in the analysis of the pindolol effect. Blood pressure and pulse rates were not significantly affected. There was slight evidence of pindolol in one eye affecting the contralateral eye but little evidence of persistence of hypotensive effects after cessation of treatment.

Double-masked cross-over comparison of Ganda 1.02 (guanethidine 1% and adrenaline 0.2% mixture) with gutt. adrenaline 1% (Simplene 1%) and with pilocarpine 1% (Sno-Pilo 1%).

A trial of the efficacy of low-concentration nonmiotic therapy was carried out, the aim being to minimise the side effects produced by 1% adrenaline or pilocarpine. A total of 77 eyes with open-angle glaucoma were studied in both parts of the trial. Thirty-nine eyes had a base-line pressure of over 28 mmHg and 28 eyes a pressure of 30 mmHg or over. In the comparison between Ganda 1.02 and adrenaline 1% (Simplene) the mean lowering of intraocular pressure was 8.6 mmHg with Ganda and 7.69 mmHg with Simplene. In the comparison between Ganda 1.02 and pilocarpine 1% (Sno-Pilo) the mean decrease was 6.34 mmHg with Ganda and 6.13 mmHg with Sno-Pilo. The resulting falls in intraocular pressure were highly significant statistically, but the differences between the effects of the 3 drugs were not significant. No significant side effects were reported with Ganda 1.02, and in particular no ptosis or superficial punctate staining of the cornea was noted.

A long term study of low concentration guanethidine and adrenaline therapy in glaucoma.

A long term study was undertaken to evaluate the efficacy of combined guanethidine (1%) and adrenaline (0.05-0.5%) therapy in controlling intra-ocular pressure in 89 patients with chronic open angle glaucoma, in whom ocular tensions proved difficult to control on miotics and/or carbonic anhydrase inhibitors. Visual acuity, fields of vision, applanation tension, size of the pupil, anterior chamber depth and gonioscopic examination of the angle were recorded before and during treatment. The follow-up extended over a period of 12 to 42 months, the mean being 28 months. The combined therapy was found to lower the intra-ocular pressure significantly in a large number of patients and the most potent combination was guanethidine 1% and adrenaline 1/4% and the average fall of intraocular pressure with the combined therapy was around 8 mm Hg. Intolerance to the combined preparation was noticed in three patients during a period of 12-18 months with the symptoms of sore eyes, conjunctival hyperaemia and lid irritation of such severity that the treatment had to be withdrawn. Resistant to treatment developed in four patients during a period of 12-36 months and treatment had to be changed. Addition to guanethidine (1%) and adrenaline up to 1/4% to pilocarpine therapy (2-4%) in eyes with narrow angles did not result in any appreciable change of the width of the angle, the size of the pupil and the depth of the anterior chamber.

Colour vision in patients with chronic simple glaucoma and ocular hypertension.

Normal subjects and patients with chronic simple glaucoma and ocular hypertension were examined with the Farnsworth-Munsell 100 hue test. Two groups of glaucoma patients were studied, one group having field defects in both eyes and the other being 'unilateral' in the sense that one eye had a full visual field. The stage of the disease was assessed by the amount of field loss or by the amount of optic disc damage as expressed by the vertical cup:disc ratio. Hue discrimination in eyes with glaucomatous field defects was worse than in eyes of normal subjects, but there was no clear indication of one range of colours being more affected than another. In glaucoma patients with field defects in both eyes the difference in error scores between the 2 eyes was greater than in normal subjects. There was a significant correlation between the degree of impairment of hue discrimination, expressed as the error score, and the amount of glaucomatous field loss. There was also a significant correlation between error score and the amount of glaucomatous damage to the optic disc, expressed by the vertical cup:disc ratio. Findings in a group of patients with ocular hypertension suggested that some of these were cases of incipient glaucoma.

Addition of timolol maleate to routine medical therapy: a clinical trial.

A double-blind cross-over trial of timolol maleate (Timoptol) while routine medical therapy was continued gave the result that pressure was reduced by 3.22 mmHg is compared to placebo and 5.01 compared to pre-timolol levels in 24 patients. There was also a small (1.858 mmHg) drop in pressure in placebo treated eyes, a small and statistically significant drop in resting pulse rate, 76.67 to 71.39/min, and a small but not statistically significant drop in diastolic blood pressure.

Immunological investigations in chronic simple glaucoma.

Serum immunoglobulins and antinuclear antibodies were estimated in 225 patients, including cases of chronic simple glaucoma, "low tension glaucoma", and ocular hypertension. The results showed that, while the mean levels of immunoglobulins Ig A and Ig M were not significantly higher in patients with glaucoma than a control series of normal adults, the mean level of Ig G was higher in those with chronic simple glaucoma. There was no clear relationship between Ig G levels and the severity of the disease as judged by the visual fields and optic disc changes. Antinuclear antibodies were found in a larger proportion of patients with chronic simple glaucoma and ocular hypertension as compared to the normal population, but there was no correlation with the severity of the disease. The incidence of other non-organ-specific and organ-specific autoantibodies was not significantly different from that of the control group. Although these results suggest an association of raised levels of Ig G and a higher incidence of antinuclear antibodies in patients with glaucoma, the evidence is insufficient to suggest that disorders of the immune system have an aetiological significance in chronic simple glaucoma.