Electroretinogram of the frog during embryonic development.

Eyes removed from frog embryos at various stages of development gave a definite pattern of change in the electroretinogram. From the 7th to 9th days the electroretinogram consisted of slow, purely cornea-negative potentials. From the 9th to 10th days the responses were negative but included a prominent fast, negative component superimposed on the slow potentials. During the 11th to 17th days positive potentials appeared and developed. From the 20th day on, the typical electroretinogram of the adult obtained.

Organization of the canine gene encoding the E isoform of retinal guanylate cyclase (cGC-E) and exclusion of its involvement in the inherited retinal dystrophy of the Swedish Briard and Briard-beagle dogs.

Intracellular cyclic GMP concentration is known to change in response to a wide variety of agents, including hormones, neurotransmitters or light. In vertebrate photoreceptors, different membrane-bound guanylate cyclase isoforms are responsible for cGMP synthesis and thus directly involved in termination of light signalling via the phototransduction cascade and recovery of the dark state. We have characterized a 4.7 kb long cDNA for the canine retinal guanylate cyclase isoform E (cGC-E) predicting a polypeptide of 1109 amino acids. The genomic structure and the complete sequence of the canine GC-E gene, which consists of 20 exons and spans about 14.5 kb, has also been determined. Northern blot analysis showed that GC-E was expressed in the canine retina as a 4.7 and 6.1 kb large transcript. RT-PCR analysis also detected low expression in cerebrum (occipital lobe). We performed a sequence analysis of the cGC-E gene in animals of a Swedish Briard and Briard-Beagle dog kinship in which an inherited retinal dystrophy is segregating. Several intragenic DNA polymorphisms were identified and used for segregation analysis which excluded cGC-E as a candidate gene for this type of canine retinal dystrophy.

Characterization of canine rod photoreceptor cGMP-gated cation channel alpha-subunit gene and exclusion of its involvement in the hereditary retinal dystrophy of Swedish Briards.

The nucleotide sequence of the canine rod photoreceptor cGMP-gated cation channel alpha-subunit (cCNCG1) cDNA has been determined. The open reading frame consists of 2073 nucleotides, which encode a putative protein of 691 amino acids. In addition, we have established the exon/intron boundaries of the cCNCG1 gene and determined the complete sequence of six introns of a total of eight. The exon/intron organization (location and length of exons and introns) of the cCNCG1 gene is very similar to that of the human rod photoreceptor cGMP-gated cation channel alpha-subunit gene. We used single-strand conformation polymorphism analysis to search for potential pathogenic sequence changes in the cCNCG1 gene in a Swedish Briard and Briard-Beagle dog kindred, in which an autosomal recessive retinal dystrophy is segregating, a disease which shows phenotypic similarities to retinitis pigmentosa, a heterogeneous group of hereditary and progressive retinal degeneration in human. In intron 3, we found several DNA polymorphisms, which do not cosegregate with the affected status of the dogs, thus excluding cCNCG1 as a candidate gene for the retinal dystrophy in this strain of Swedish Briards.

Lipofuscin-formation in retinal pigment epithelial cells is reduced by antioxidants.

The accumulation of lipofuscin by retinal pigment epithelium may be an important feature in the pathogenesis of age-related macular degeneration, suggesting the possibility that this common cause of blindness might be prevented or delayed by antioxidants. In support of this idea, we now report significantly reduced formation of lipofuscin when the antioxidant substances lutein, zeaxanthin, lycopene (carotenoids), or alpha-tocopherol were added to rabbit and bovine (calf) retinal pigment epithelial (RPE) cells exposed to normobaric hyperoxia (40%) and photoreceptor outer segments. Rabbit and calf RPE cells were grown for 2 weeks with addition of one of the test substances every 48 h. The cellular uptake of carotenoids and alpha-tocopherol was assayed by HPLC after 2 weeks. The lipofuscin-content was measured by static fluorometry (rabbit cells) or by image analysis (calf cells). Both rabbit and calf RPE showed similar results with significantly lower amounts of lipofuscin in antioxidant-treated cells. The effect of carotenoids is especially interesting, since the result is not dependent on their protective effect against photo-oxidative reactions. The chain-breaking abilities of these antioxidants in peroxidative reactions of lipid membranes and quenching of free radicals seem to be of importance for inhibition of lipofuscin formation.

Lipofuscin-formation in cultured retinal pigment epithelial cells is related to their melanin content.

Age-related macular degeneration (AMD), the leading cause of blindness in the developed world, is accompanied by degeneration of the retinal pigment epithelial (RPE) cells. There is an inverse correlation between the melanin content of the eye and the incidence of AMD. Lipofuscin (LF)-accumulation in RPE cells accompanies the process of aging, and may also be related to AMD. This study was designed to evaluate the effect of melanin/melanosomes on the rate of LF formation in cultured rabbit and bovine RPE cells subjected to oxidative stress (40% normobaric O(2)) and daily supplementation with photoreceptor outer segments for 4 weeks. The LF content was measured at 0, 2, and 4 weeks in RPE cells from pigmented and albino rabbits, as well as in pigment-rich and pigment-poor bovine cells. Albino rabbit and pigment-poor bovine cells accumulated significantly higher amounts of LF than pigmented rabbit cells and pigment-rich bovine RPE cells after both 2 and 4 weeks of exposure. Autometallography of melanin-containing cells, without previous exposure to ammonium sulfide, showed a positive outcome, indicating either the occurrence of pre-existing iron-sulphur clusters or an extremely high intrinsic reducing capacity. These results suggest that melanin acts as an efficient antioxidant, perhaps by interacting with transition metals.

Lipofuscin accumulation in cultured retinal pigment epithelial cells causes enhanced sensitivity to blue light irradiation.

Lipofuscin accumulates with age within secondary lysosomes of retinal pigment epithelial (RPE) cells of humans and many animals. The autofluorescent lipofuscin pigment has an excitation maximum within the range of visible blue light, while it is emitting in the yellow-orange area. This physico-chemical property of the pigment indicates that it may have a photo-oxidative capacity and, consequently, then should destabilize lysosomal membranes of blue-light exposed RPE. To test this hypothesis, being of relevance to the understanding of age-related macular degeneration, cultures of heavily lipofuscin-loaded RPE cells were blue-light-irradiated and compared with respect to lysosomal stability and cell viability to relevant controls. To rapidly convert primary cultures of RPE, obtained from neonatal rabbits, into aged, lipofuscin-loaded cells, they were allowed to phagocytize artificial lipofuscin that was prepared from outer segments of bovine rods and cones. Following blue-light irradiation, lysosomal membrane stability was measured by vital staining with the lysosomotropic weak base, and metachromatic fluorochrome, acridine orange (AO). Quantifying red (high AO concentration within intact lysosomes with preserved proton gradient over their membranes) and green fluorescence (low AO concentration in nuclei, damaged lysosomes with decreased or lost proton gradients, and in the cytosol) allowed an estimation of the lysosomal membrane stability after blue-light irradiation. Cellular viability was estimated with the delayed trypan blue dye exclusion test. Lipofuscin-loaded blue-light-exposed RPE cells showed a considerably enhanced loss of both lysosomal stability and viability when compared to control cells. It is concluded that the accumulation of lipofuscin within secondary lysosomes of RPE sensitizes these cells to blue light by inducing photo-oxidative alterations of their lysosomal membranes resulting in a presumed leakage of lysosomal contents to the cytosol with ensuing cellular degeneration of apoptotic type. The suggested mechanism may have bearings on the development of age-related macular degeneration.

Progressive retinal atrophy in the Abyssinian cat. Electron microscopy.

Seven adult Abyssinian cats at different stages of a recessively inherited retinal degenerative disease (progressive retinal atrophy) were studied ultrastructurally. At the stage of early disease, in 2-yr-old cats, disorganized and vesiculated discs were found in less than half of the rod outer segments in the periphery, while similar changes were seen in the central retina only infrequently or in patches. Cones appeared normal in all areas of the retina at the early stage. With progression of disease, the lesions were more advanced in all areas of the retina, and involved both rods and cones, with the most severe alterations found in the midperiphery. At the advanced stage, in a 6-yr-old cat, both rods and cones were lost, the inner nuclear layer thus being separated from the pigment epithelium by Müller cell processes and a few remaining outer plexiform processes only. Remnants of photoreceptor outer and inner segments, macrophages, and what appeared to be displaced photoreceptor cell nuclei could be found occasionally in the subretinal space, however. Clumps of pigment granules were often observed in the photoreceptor layer in the non-tapetal fundus. The pigment epithelium remained morphologically intact as a single layer of uninterrupted cells throughout the disease process, as did tapetal cells and choriocapillaris. There was no difference in the severity of disease between the peripheral tapetal and non-tapetal fundus. In the inner retina, only minor alterations were observed. These changes appeared at a later time than photoreceptor degeneration, and were considered secondary to the latter.

Effects of intravitreally injected DL-alpha-aminoadipic acid on the c-wave of the D.C.-recorded electroretinogram in albino rabbits.

The D.C. electroretinogram of four adult albino rabbits was studied 13.5 to 15 hr after injection of 0.1 ml of 0.15M DL-alpha-aminoadipic acid (alpha-AAA) into the vitreous body of one eye. The other eye was similarly injected with saline and served as control. In the alpha-AAA--treated eye the b-wave was markedly reduced or absent and the a- and c-waves increased compared with the control eye. Sincs alpha-AAA damages the Müller cells, the results support the view that these cells are related to the generation of the b-wave and to the negative slow PIII-potential, which modifies the positive pigment epithelial component of the c-wave.

Visual pigment and visual receptor cells in fetal and adult sheep.

The visual pigments, and the structure of the visual cells, were investigated by spectrophotometry and by light and electron microscopy in fetal and adult sheep. The rhodopsin system in adult sheep closely resembles that of cattle. The absorbance maxima of rhodopsin, lumirhodopsin, and metarhodopsin I are at 498, 490, and 480 nm, respectively. The estimated molar absorbance coefficient at the wavelength of maximum absorption of rhodopsin is 40,000M-1 . cm-1. Rhodopsin was detected from a fetal age of 85 days (term at 145 days). Partial bleaching of extracts from fetal eyes (95, 105, and 115 days) did not demonstrate cone pigments, although cones were present in fair numbers at a fetal age of about 105 days. The time course of rhodopsin formation between 85 and 140 days resembles a growth curve. The amount of rhodopsin shortly before birth (140 days) is about 0.6 times that in the adult. The number and dimensions of rod outer segments as well as packing of the discs were studied structurally and related to the rhodopsin content. A fairly good correlation was found at the earliest stages (95 and 105 days gestation age), when rhodopsin concentration was very low and rod outer segments were few and small, as well as at the latest stage (140 days). At 115 days the rhodopsin content observed by spectrophotometry was less than that indicated by the outer segment volume, probably mainly due to the outer segment discs and possibly to the rhodopsin molecules being less tightly packed than at 140 days.

Studies on the retina and the pigment epithelium in hereditary canine ceroid lipofuscinosis. IV. Changes in the electroretinogram and the standing potential of the eye.

The present study correlates ultrastructural abnormalities in the retinal pigment epithelium (RPE) with electrophysiologic changes demonstrated in examinations of dogs with canine ceroid-lipofuscinosis (CCL) at various stages of clinical involvement using dc electroretinograms (ERG), including the c-wave, as well as recordings of the variations of the standing potential (SP) of the eye, both of which reflect the activity of the pigment epithelium. Normal c-waves and SP variations were seen at early stages of disease. At later stages, specific signs of pigment epithelial impairment were found in the form of (1) markedly reduced SP variations, (2) an increase in amplitude of the trough after the b-wave, and (3) a disappearance of the c-wave, which was replaced by a negative potential. These ERG changes correlate very well with a damaged pigment epithelium that generates the positive potential of the c-wave, as well as with normal Müller cells that generates the negative potential coinciding in time with the c-wave, and contributing to the trough after the b-wave. In the end-stage of the disease all potentials of the ERG were reduced drastically, evidently as a sign of cessation of neuroretinal function. Similarities between English setters with CCL and human Batten disease are discussed.

The in vitro frog pigment epithelial cell hyperpolarization in response to light.

Pigment epithelial cell membrane potentials were measured in an in vitro frog retina-pigment epithelium-choroid preparation. Light stimuli hyperpolarized the apical membrane of the pigment epithelium. This hyperpolarization was the source of the c-wave of the electroretinogram. Light stimuli also decreased retinal extracellular potassium ion concentration, [K+]O, with the same time course as the apical hyperpolarization. It is suggested that the pigment epithelial hyperpolarization, which causes the c-wave, results directly from the light-evoked decrease in retinal [K+]O.

Lipofuscin formation in cultured retinal pigment epithelial cells exposed to photoreceptor outer segment material under different oxygen concentrations.

Lipofuscin accumulates in the course of time in the acidic vacuolar apparatus of retinal pigment epithelial (RPE) cells and may influence their metabolic functions. In order to study the effect of oxidative stress on lipofuscin accumulation, rabbit RPE cell cultures were kept at an ambient oxygen concentration of either 8% or 40%. To simulate the normal phagocytic function of RPE cells, bovine photoreceptor outer segments (POS) were added daily. The lipofuscin-specific autofluorescence was measured after 1, 2 and 3 weeks. RPE cells cultured under normobaric hyperoxic conditions (40% oxygen) showed significantly higher levels of lipofuscin-like autofluorescence than those kept under normobaric and probably normoxic conditions (8% oxygen) after 1 (p = 0.0050), 2 (p = 0.0001) as well as 3 (p = 0.0077) weeks. At both oxygen concentrations, the lipofuscin accumulation level was increased after 2 weeks of POS exposure (40% p = 0.0001; 8% p = 0.0037) and even further after 3 weeks (40% p = 0.0541; 8% p = 0.0377). The results suggest an involvement of oxidative mechanisms in the formation of lipofuscin from phagocytized POS by RPE cells. The autofluorescence of control cells, not exposed to POS, was significantly (40%: 1 week p = 0.0011, 2 weeks p = < 0.0001, 3 weeks p = 0.0001; 8%: 1 week p = 0.0036, 2 weeks p = 0.0063, 3 weeks p = 0.0066) lower than that of the POS-fed cells. The autofluorescence increased significantly (40% p = 0.0059; 8% p = 0.0034) between week 1 and week 3 in the control cells. This finding may reflect a contribution to lipofuscin formation by autophagocytized intracellular material. The present model seems to be useful for further studies on the mechanisms behind lipofuscinogenesis of RPE cells as well as the possible effects of lipofuscin accumulation on cell functions and viability.

Formation of lipofuscin in cultured retinal pigment epithelial cells exposed to pre-oxidized photoreceptor outer segments.

Accumulation of lipofuscin in the retinal pigment epithelium (RPE) with increasing age may affect essential supportive functions for the photoreceptors. Earlier, we described a model system for the study of lipofuscinogenesis in RPE cell cultures and showed that mild oxidative stress enhances lipofuscin formation from phagocytized photoreceptor outer segments (POS). In the present study, bovine POS were photo-oxidized, and turned into a lipofuscin-like material, by irradiation with UV light. Transmission electron microscopy of irradiated POS showed loss of the normal stacks of the disk membranes with conversion into an amorphous osmiophilic electron-dense mass. The formation of thiobarbituric acid reactive substances (TBARS), estimated during the irradiation process, indicated lipid peroxidation. Irradiated POS also showed a strong granular yellow autofluorescence. RPE cell cultures, kept at 21% ambient oxygen, were fed daily for 3, 5 or 7 days with either (i) UV-peroxidized POS, (ii) native POS or (iii) culture medium only. RPE cells fed irradiated POS showed significantly higher levels of lipofuscin-specific autofluorescence compared to cells exposed to native POS after 3 days (p = 0.0056), 5 days (p = 0.0037) and 7 days (p = 0.0020), and to the non-exposed control cells (3 days: p = 0.005, 5 days: p = 0.0037, 7 days: p = 0.0094). The lipofuscin content of cells exposed to irradiated POS increased significantly between days 3 and 7 (p = 0.0335). Ultrastructural studies showed much more numerous and larger lipofuscin-like inclusions in RPE cells fed irradiated POS compared to cells exposed to native POS. In the control cells, lipofuscin-like granules were small and sparse. It appears that exposing RPE cells to previously peroxidized POS, thus artificially converted to lipofuscin and obviously not digestible by the lysosomal enzymes, accelerates the formation of severely lipofuscin-loaded cells. The results will be useful for further studies of possible harmful effects of lipofuscin in heavily loaded RPE cells.

Interaction of PhXA41, a new prostaglandin analogue, with pilocarpine. A study on patients with elevated intraocular pressure.

OBJECTIVE: To evaluate the effects of PhXA41, a new prostaglandin analogue, on the intraocular pressure (IOP) in patients receiving pilocarpine treatment and the effects of pilocarpine in patients receiving PhXA41 treatment. DESIGN: Twenty patients with ocular hypertension were randomized into two parallel groups. The treatment period was 2 weeks. Ten patients in group 1 were given PhXA41 twice daily during week 1 and, in addition, pilocarpine three times daily during week 2. Ten patients in group 2 received pilocarpine three times daily during week 1 and PhXA41 twice daily in addition during week 2. PhXA41 was used in a concentration of 0.006%, and pilocarpine was given in a concentration of 2%. MAIN OUTCOME MEASURES: In group 1, the mean IOP on day 0 was 25.1 mm Hg; on day 7, 19.1 mm Hg; and on day 14, 17.6 mm Hg. In group 2, the mean IOP on day 0 was 23.8 mm Hg; on day 7, 20.4 mm Hg; and on day 14, 17.7 mm Hg. RESULTS: PhXA41 had a clinically significant IOP-lowering effect (23.4% reduction on day 7 as compared with baseline day (P < .001). The corresponding value with pilocarpine was 14.3% (P < .001). When pilocarpine was added to PhXA41, the additional IOP reduction was 7.4% (P < .01) compared with 14.2% (P < .01) when PhXA41 was added to pilocarpine. The two groups were found to have an almost equal reduction in IOP on day 14 (group 1, 29.4%; group 2, 26.6%). No serious adverse reactions were seen. Some conjunctival hyperemia in the PhXA41-treated eyes was noted on day 7, as compared with the pilocarpine-treated eyes, but there were few complaints of discomfort. CONCLUSIONS: This study indicated that PhXA41 could be useful in the treatment of glaucoma, as monotherapy, or in certain cases in combination with pilocarpine.

Dose response and duration of action of dorzolamide, a topical carbonic anhydrase inhibitor.

The multiple-dose, dose-response relationship and duration of action of the novel topical carbonic anhydrase inhibitor dorzolamide (previously known as MK-507) were investigated in a double-masked, randomized, placebo-controlled, parallel study in 73 patients with bilateral primary open angle glaucoma or ocular hypertension. Dorzolamide (0.7%, 1.4%, or 2%) or placebo was administered every 12 hours for 5 days and then every 8 hours for 7 days. Intraocular pressure was investigated with multiple 12-hour diurnal curves. All concentrations of dorzolamide demonstrated substantial lowering of intraocular pressure throughout the day when given twice daily (9% to 21%) or three times daily (14% to 24%). Although a dose-dependent response was observed immediately following the first dose, there were no significant differences between concentrations or dose response at either the twice or three times daily dosing regimen. Three times daily administration of 2% dorzolamide demonstrated a mean percent decrease in intraocular pressure of 18% to 22% throughout the day (mean decrease, 4.5 to 6.1 mm Hg). Dorzolamide appears to have substantial potential in the treatment of glaucoma and ocular hypertension.

Electrophysiological responses related to the pigment epithelium and its interaction with the receptor layer.

The standing potential (SP) of the eye is generated mainly at the apical surface of the pigment epithelium, where tight junctions between adjacent cells create a high resistance membrane. It can be recorded indirectly by means of the electrooculogram (EOG) or directly by recording between electrodes connected to the cornea and the forehead. Changes in illumination provoke slow SP changes in the form of damped oscillations with a frequency of about 2/hour. These oscillations are abolished or substantially reduced in pigment epithelial diseases, such as retinitis pigmentosa and vitelline macular degeneration. The c-wave of the electroretinogram (ERG) represents the hyperpolarization mainly of the apical membrane of the pigment epithelial cells that occurs in response to a decrease in potassium ion concentration in the extracellular space of the receptor layer induced by light stimulation. When repeatedly recorded the amplitude of the c-wave oscillated with time in the same way as the SP. The c-wave is abolished or markedly reduced in pigment epithelial disorders. The negative h-wave of the off-ERG shows such extensive similarities to the c-wave of the on-ERG that it seems to represent the reversal of the processes in the pigment epithelium - receptor complex underlying the c-wave.

Effects of argon (green) laser treatment of soft drusen in early age-related maculopathy: a 6 month prospective study.

AIM: To evaluate whether perifoveal laser photocoagulation of soft drusen reduces the total area occupied by drusen. METHOD: In a prospective, randomised study, 20 patients (mean age 71.3 (SD 7.7) years) with early age-related maculopathy (ARM) in the form of soft drusen and pigmentary changes and with good visual acuity (0.94 (0.09)) were treated with argon green laser photocoagulation. Mild laser burns (200 microns) were placed within a temporal horseshoe-shaped area, extending from a distance of no less than 500 microns from the centre of the fovea to the vascular arcades. They were placed on the drusen and scattered over areas where no drusen were present. Fundus colour photography and fluorescein angiography were performed at study entry as well as after 3 and 6 months. Nineteen age-matched patients (68.5 (6.2) years) with soft drusen maculopathy (visual acuity 0.95 (0.10)) were followed as a control group. Using a computer system, the area occupied by drusen was determined as a portion of the total area of a circle with a radius corresponding to 1250 microns in the fundus for the angiograms and 2500 microns for the colour photographs, respectively. At study entry, the mean area occupied by drusen in the treatment group was not significantly (p > 0.5-0.7) different from that of the control group. RESULTS: The mean drusen area of the angiograms and fundus colour photographs in the treated group decreased significantly from 19.3% to 13.8% (p = 0.002) and from 7.84% to 5.02% (p = 0.005), respectively. In the untreated group, the mean area occupied by drusen increased significantly from 17.4% to 20.4% (p = 0.030) and from 8.33% to 9.23% (p = 0.002), respectively. No significant changes in visual acuity (p > 0.05-0.5) or in visual fields (p > 0.05-0.3) occurred in either of the two groups during 6 months. CONCLUSION: The study suggests that the area occupied by soft drusen in patients with early ARM decreases after perifoveal laser photocoagulation but increases in an untreated control group.

Prophylactic laser treatment in early age related maculopathy reduced the incidence of exudative complications.

AIM: To investigate the effect of prophylactic laser treatment on drusen area and incidence of exudative lesions in patients with soft drusen maculopathy. METHODS: In a prospective study, patients with early age related maculopathy (ARM) and good visual acuity were randomized to laser treatment or to a control group. Each group consisted of two subgroups: a fellow eye group and a bilateral drusen group. At 3 years, 36 of 38 enrolled patients remained in the study. Photocoagulation was performed with an argon green laser, approximately 100 mild laser burns being placed on and between the drusen in a perifoveal temporal horseshoe-shaped area. Both cases and controls were subjected to fundus colour photographs and fluorescein angiograms at regular intervals, and the drusen area was calculated in both photographs and angiograms. At baseline, there were no significant differences (p > 0.3-0.8) in drusen area between the groups. RESULTS: In the treatment group, mean drusen area decreased significantly in the fundus photographs as well as in the angiograms (p < 0.001). Visual acuity and colour contrast sensitivity (CCS) did not change significantly. All these results are valid also for the subgroups. In the control group, however, mean drusen area increased significantly (p < 0.001). Mean visual acuity decreased significantly (p < 0.01) as did the colour contrast sensitivity along the tritan axis (p = 0.02). For the fellow eye control group (n = 7), the increase in drusen area in fundus photographs and the decrease in CCS along the tritan axis were not statistically significant (p = 0.57 and p = 0.37, respectively). Furthermore, at 3 years, five patients in the control group showed exudative lesions (1/7 in the fellow eye group and 4/12 in the bilateral drusen group), whereas no such complications occurred in the treatment group. One patient developed a small atrophy, however. Thus, there is now a significant difference (p = 0.047), however with a large 95% confidence interval, 0.06-0.46, regarding exudative complications between the treated group and the control group in our small patient material. CONCLUSION: Perifoveal mild laser treatment causes a reduction in drusen area in patients with soft drusen maculopathy and may lower the incidence of exudative lesions.

A double masked comparison of the intraocular pressure reducing effect of latanoprost 0.005% and 0.001% administered once daily in open angle glaucoma and ocular hypertension.

AIM: To compare the intraocular pressure (IOP) reducing effect of latanoprost 0.005% and 0.001%. METHODS: Twenty four patients with glaucoma or ocular hypertension were randomised into two groups. Twelve patients (group 1) were given latanoprost 0.005% once daily for 4 weeks and then latanoprost 0.001% once daily for the following 4 weeks. Twelve patients (group 2) were given latanoprost 0.001% once daily for 4 weeks and then latanoprost 0.005% for the following 4 weeks. RESULTS: There was a significant IOP reduction from baseline in both groups on day 28 as well as on day 56. When the results from both groups were used for calculations, the mean IOP reduction from baseline after 4 weeks of treatment with latanoprost 0.005% (day 28 or 56) was 9.6 (SD 3.3) mm Hg (35.0%). After 4 weeks of treatment with latanoprost 0.001%, the IOP reduction (day 28 or 56) was 7.6 (3.4) mm Hg (27.7%). The difference in IOP reduction between the two concentrations was 2.0 (2.3) mm Hg (p < 0.001). CONCLUSIONS: Latanoprost 0.005% was more effective than latanoprost 0.001% in reducing IOP. Even the lower concentration was surprisingly effective, and potentially may be of importance for use in clinical practice. Furthermore, it is at present unknown whether the increase in iris pigmentation seen in certain patients treated with latanoprost 0.005% is dose dependent and might be less pronounced with latanoprost 0.001%. Long term studies with a larger number of patients are required in order to answer this question.

Corneal thickness response to high and low water content lenses in aphakic eyes.

A high water content lens (Scanlens 75, +14.5 dioptres) and a low water content lens (Bausch and Lomb Soflens H3, +14.5 dioptres) were compared with respect to corneal thickness response after 6 hours of wear in a provocative test on 12 aphakic eyes. The mean increase in central corneal thickness was 3.3% for Scanlens and 6.4% for Soflens. This difference is statistically highly significant (p less than 0.001). There seems to be a correlation between the response to Scanlens and that to Soflens when the responses of each eye were plotted against each other. Average lens thickness correlated somewhat better with corneal thickness increase than did central lens thickness.