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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.

Purpose: To determine efficacy and safety of latanoprost, a prostaglandin analog for glaucoma, during 1 year of treatment. Methods: After baseline measurements, 0.005% latanoprost was topically applied once daily for 12 months in patients from Scandinavia, the United Kingdom, and the United States who had elevated intraocular pressure (IOP). Diagnoses included ocular hypertension, chronic open-angle glaucoma, exfoliation syndrome, and pigment dispersion syndrome. Treatment was masked for the first 6 months and open-label during the second 6 months. Results: Of the 272 patients initially enrolled, withdrawals were due to inadequate IOP control (1 %), increased iris pigmentation (5%), other ocular problems (3%), systemic medical problems (3%), and nonmedical reasons (14%). Latanoprost significantly ( P Conclusion: Latanoprost safely and effectively reduces IOP for 1 year in patients of diverse nationalities, providing further evidence for its usefulness in chronic glaucoma therapy.

Purpose: To investigate the intraocular pressure (IOP)-reducing effect and side effects of PhXA41, a new prostaglandin F 2α (PGF 2α ) 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 µg/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.

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 (10P) 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 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.

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.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.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.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.

Seizures represent the most distinctive sign of neurologic disease in the neonate. The definitive method to identify seizures is based on the visual analysis of the electroencephalogram (EEG). Reliable seizure detection in neonates can optimize clinical treatment and theoretically reduce brain injury. Most efforts in computerized, automated seizure detection have been directed towards adults and hence commercially available schemes are not specifically focused on neonatal seizure detection. As in adults, the normal spectrum of neonatal EEG follows an inverse power-law attenuation over a band of clinically relevant frequencies suggestive of self-similar fluctuations over a multiplicity of scales. In this paper, measures to monitor the scaling property of the neonatal EEG to detect electrographic seizures are proposed. This is achieved by multi-scale analysis of the signal using the wavelet transform as a tool. A seizure detection scheme which can be implemented on-line is proposed. The test set included data from five neonates of 36-42 weeks conceptional age. Preliminary tests on 18 channels of data from 5 patients yielded 95.9% seizure detection rate. The detection rate is 100% when the analysis is based on multichannel data.

The additivity, safety and acceptability of brimonidine (0.2% b.i.d.) versus pilocarpine (2.0% t.i.d.) were compared in 141 patients whose intraocular pressure (IOP) was inadequately controlled on beta-blocker monotherapy. Brimonidine and pilocarpine demonstrated equivalent additive ocular-hypotensive efficacy at peak and trough drug effect at every study visit. The overall mean additive IDP-lowering effects were 5.0 mmHg and 3.7 mmHg at peak and trough for brimonidine, respectively, and 4.5 mmHg and 2.9 mmHg at peak and trough for pilocarpine, respectively. Significantly more patients reported visual disturbance, headache and had worsening of far visual acuity in the pilocarpine group, while significantly more patients reported dry mouth in the brimonidine group. Thus, in addition to a highly favourable clinical safety and efficacy profile as monotherapy for ocular hypertension and open-angle glaucoma, brimonidine (0.2% b.i.d.) is also safe and effective when used adjunctively with a beta-blocker, producing an additive IOP lowering effect equivalent to that of pilocarpine but with fewer adverse ocular effects and better patient acceptability.

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.

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.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.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 (P0.011). 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.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.

The long term effects of two dose regimens of latanoprost (PhXA41) administered to eyes concomitantly treated with timolol which had not adequately been controlled by timolol alone were compared. A total of 50 patients, 17 with primary open angle glaucoma and 33 with capsular glaucoma, were recruited from five clinics. All had glaucomatous visual field defects and an intraocular pressure (IOP) of at least 22 mm Hg despite treatment with 0.5% timolol twice daily. Patients were randomised to two treatment groups. In one group 0.006% latanoprost was given twice daily, in the other group placebo was given at 8 am and latanoprost at 8 pm for 3 months, with concomitant timolol treatment in both groups. Average daytime IOP (mean (SD)) at baseline (on timolol alone) and after 4 and 12 weeks' treatment was 24.8 (3.6), 16.8 (4.3), and 15.7 (2.4) mm Hg respectively with once daily application of latanoprost and 24.9 (2.9), 18.1 (3.0), and 18.0 (3.6) mm Hg respectively with latanoprost twice daily. No clinically significant side effects were observed during treatment. Latanoprost causes a marked and sustained IOP reduction in eyes which are also being treated with timolol. Latanoprost given once daily is at least as effective and probably superior to a twice daily dose regimen.

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.

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 in 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.

Total outflow facility was measured using the technique of constant pressure infusion over the range 20–35 mm Hg. The mean value in control animals was 0.33–0.35 μ l/min/mm Hgbut thi

The present experiments were undertaken in order to see whether natural and synthetic vasopressins alter the rate of active sodium transport in vitro under conditions independent of blood supply using a preparation of isolated ciliary body from the rabbit and measuring changes of trans-epithelial short-circuit current the chief component of which (at least in this species) is the “active” sodium flux (Cole, 1962). Preliminary studies were also made on the effects of catecholamines, pilocarpine, acetylcholine and prostaglandins E1 and F2α. The iris/ciliary body preparation from albino rabbits was mounted between 2 chambers containing modified Krebs' medium and maintained at 37°C. Trans-epithelial potential was recorded under open-circuit conditions throughout the experiment and short-circuit current was measured at intervals of 5 to 15 min. After an initial control period the drug under investigation was added to the medium on the cameral side of the tissue and the measurements continued for a further 15 to 30 min before repeating the procedure at the next higher dose-level. Three or four different concentrations were used with each preparation and the responses, expressed as percentage change of short-circuit current from mean control value were used to derive dose/response curves. The substances used were natural vasopressin, lysine8-vasopressin, phenylalanine2-lysine8-vasopressin and ornithine8-vasopressin, l-noradrenaline bitartarate, isoprenaline hydrochloride, pilocarpine, nitrate, prostaglandins E1 and F2α (Upjohn) and 3′5′ adenosine monophosphate. Natural vasopressin and Lys8-vasopressin both caused significant increases of short-circuit current at concentrations less than 10 μU/ml. The 2 other substances were less active, Orn1-vasopressin being effective only at 105 μU/ml. On the basis of their effectiveness in stimulating active transport in the present experiments the 4 substances may be placed in the following order: “Pitressin” ≙ Lys8-vasopressin > Phe2Lys8-vasopressin > Orn8-vasopressin which would accord with their ranking in order of antidiuretic activity. Neither catecholamines pilocarpine or acetylcholine showed direct inhibitory action on active transport and it is suggested that any ocular hypotensive action is due to haemodynamic changes or to alterations of outflow facility. The prostaglandins stimulated short-circuit current but cyclic-AMP had little consistent action. If, as these findings indicate, active transport across the ciliary epithelium can be stimulated by vasopressin concentrations within the normal physiological range of 1 to 10 μU/ml, it seems reasonable to infer that in intact animals, the level of endogenous vasopressin production may be significant in regulating the rate of aqueous humour formation.

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.

The development of ideas about the genesis of glaucoma passed a major milestone when Barkan used gonioscopic appearances of the anterior chamber angle to separate the Primary glaucoma’s into “open” and “closed” varieties. Recognition of “pupil block” as a major cause of angle closure glaucoma and its relief by means of an iridectomy (Curran 1920) explained von Graefes intermittent success with this operation and also lead to the introduction of this operation as an important part in the management of this type of glaucoma. When long term follow-up of the second eye in patients with acute primary angle closure glaucoma showed that a large proportion would also develop this disease (Lowe 1962; Edwards 1982) the concept of a “prophyllactic” iridectomy was born. However, not all “second” eyes did so progress (Lowe 1962; Mapstone 1981) and the operation was not without complications. Apart from the risks of infection, other problems described include concern about cataract formation (Go and Kitazawa 1981; Godel and Regenboga 1971; Floman et al. 1977). Until recently, however, the risks of visual loss from an acute attack (Douglas et al. 1974; McNaught et al. 1975; Sonty and Schwartz 1981) have always been felt to outweigh the risks of an operation, so patients considered “at risk” were recommended to undergo a surgical iridectomy.

A randomized double masked single dose trial of a topical preparation of acetazolamide as a 3.8% solution was carried out in 25 patients with untreated ocular hypertension. Treatment with acetazolamide eye drops resulted in a mean fall of over 4 mmHg in intraocular pressure (about 17% reduction) and the hypotensive effect was noticed for six hours, being the total duration of the study, without any local or systemic adverse effects, whilst the reduction in ocular tension observed in the placebo treated eye was only around 1 mm Hg (about 4%) and the difference was highly significant (P

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 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.

The effect of pilocarpine on visual acuity and on the dimensions of the cornea, anterior chamber, and lens were studied in two groups of subjects. Significant changes in ocular tension, corneal curvature, anterior chamber depth, and lens anterior radius were found in a group of 55 glaucomatous eyes as a result of pilocarpine treatment, but there was no change in corneal thickness. Out of 102 glaucomatous eyes 78 became relatively myopic, and this appears to be due to changes in the dimensions of the lens of the eye similar to those occurring in accommodation, as a result of the effect of the drug on the ciliary muscle. The effect of pilocarpine on anterior chamber depth, area, and volume was studied in 125 eyes using a photographic method, and a significant reduction in the dimensions of the anterior chamber was observed as a result of the administration of pilocarpine. A significant correlation between depth and volume was also noted and the implications of this are discussed.

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.

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.

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. Resistance 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.

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.

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 role of pituitary vasopressin (antidiuretic hormone--ADH) in the formation and dynamics of aqueous humour was studied in rabbits employing different techniques. Using isolated ciliary body preparations the changes in transepithelial short-circuit current were measured, and natural vasopressin and Lys8-vasopressin were found to increase the transepithelial short-circuit current at concentrations less than 10 muU/ml (i.e. within the physiological range), indicating increased sodium transport across the ciliary epithelium. In another series of experiments with intact rabbits given an ethanol load to suppress endogenous ADH, administration of exogenous vasopressin raised the intraocular pressure, and a similar effect was observed when endogenous ADH production was stimulated with nicotine. Direct measurements of outflow showed that vasopressin was without effect when given intravenously and that the only effect when given intracamerally was to increase the facility which would tend to lower rather than raise the intraocular pressure. Finally, the intra-arterial and intravenous effects of vasopressin on circulation in the iris and on the intraocular and systemic arterial pressures were studied. Local effects on the vascular bed in the eye and changes in systemic blood pressure were observed only at rates of administration well in excess of the physiological range for endogenous vasopressin production. It is concluded that, at physiological levels, antidiuretic hormone can stimulate active sodium transport into the eye thereby tending to raise the intraocular pressure, and it is suggested that this may act as a homeostatic regulating mechanism limiting changes in the rate of formation of aqueous humour and in intraocular pressure which might otherwise result from diurnal variations in the state of body hydration. This also offers some explanation for the ocular hypotensive action of ethanol.

The effects of certain vasopressins (VPs), prostaglandins (PGs) and catecholamines on active transport across the ciliary epithelium have been investigated in vitro and an attempt has been made to relate the findings to the actions of these substances in vivo. Natural VP and lysine8-VP at physiological concentrations increased the transepithelial short-circuit current in vitro and, when infused intravenously into rabbits whose endogenous VP level had been suppressed by prior administration of ethanol, caused a significant increase of ocular tension. It is suggested that in intact animals, the naturally occurring variations of endogenous VP level in the blood may play a role in the physiological regulation of intraocular pressure. PGE1, PGE2 and PGF2α stimulate short-circuit current in vitro, the E-type PGs being considerably more effective than PGF2α. The response to E1 and E2 was antagonized by low molecular weight polyphoretin phosphate although the high molecular weight fraction was inactive. The PG concentrations required to exert this in vitro effect are well above those reported as causing ocular hypertension in vivo and it is suggested that the in vivo action may be due to increased permeability of the blood aqueous barrier rather than to stimulation of epithelial transport. Noradrenaline and isoprenaline at high concentrations also increase epithelial transport in vitro but it is thought that local vasoconstriction and effects on outflow facility predominatly determine the intraocular pressure responses at concentrations used in experiments on intact animals. The object of the present contribution is to describe the effects of some pharmacological substances on active transport across the ciliary epithelium and, particularly in the case of the vasopressins, to relate this action to the physiological control of intraocular pressure (IOP) and to the known in vitro actions of certain drugs.