ZD1839 was well tolerated, with DLT observed at a dose well above that at which antitumor activity was seen. Pharmacokinetic analysis confirmed that ZD1839 was suitable for administration as a once-daily oral tablet formulation. Phase II monotherapy and phase III combination trials in NSCLC are being conducted to investigate further the efficacy, tolerability, and optimal daily dose of ZD1839.

Aim: To determine the incidence of non-severe keratitis (NSK) and severe keratitis (SK) among wearers of current generation contact lenses. Methods: A 12 month, prospective, hospital based epidemiological study was conducted by examining all contact lens wearers presenting with a corneal infiltrate/ulcer to a hospital centre in Manchester. A clinical severity matrix was used to differentiate between NSK and SK, based on the severity of signs and symptoms. The size of the hospital catchment population and the wearing modalities (daily wear (DW) or extended wear (EW)) and lens types being used were estimated from relevant demographic and market data. Results: During the survey period, 80 and 38 patients presented with NSK and SK, respectively. The annual incidences (cases per 10 000 wearers) for each wearing modality and lens type were: DW rigid-NSK 5.7, SK 2.9; DW hydrogel daily disposable-NSK 9.1, SK 4.9; DW hydrogel (excluding daily disposable)-NSK 14.1, SK 6.4; DW silicone hydrogel-NSK 55.9, SK 0.0; EW rigid-NSK 0.0, SK 0.0; EW hydrogel-NSK 48.2, SK 96.4; EW silicone hydrogel-NSK 98.8, SK 19.8. The difference in SK between EW hydrogel and EW silicone hydrogel was significant (p = 0.04). Conclusions: A clinical severity matrix has considerable utility in assessing contact lens related keratitis. There is a significantly higher incidence of SK in wearers who sleep in contact lenses compared with those who only use lenses during the waking hours. Those who choose to sleep in lenses should be advised to wear silicone hydrogel lenses, which carry a five times decreased risk of SK for extended wear compared with hydrogel lenses.

Aim-To elucidate the diurnal variation in human corneal thickness over a 48 hour period. Method-Changes in central corneal thickness were monitored in eight healthy subjects (four male, four female) aged between 10 and 63 years using an ultrasonic pachymeter. Measurements were made over a 48 hour period-immediately before sleep, immediately upon waking and at 15, 30, 45 minutes, 1, 1.5, 2, 2.5, 3 hours, and at 2 hour intervals thereafter throughout the remainder of each day. Results-The mean corneal thickness for the group (SD) was 546 (14) ptm, with a mean overnight increase of 5.5% (2.90/6) (range 1.9-12.6%) and a maximum diurnal increase of 7.2% (2.8%) (range 2.1-14.3%). Individual differences in the extent of diurnal and overnight variation occurred within the group. For three subjects, the first reading taken on waking was not the highest and corneal thickness continued to increase. Conclusion-These data confirm an increase of corneal thickness during sleep, but also reveal considerable variation during waking hours. Thus, the overnight changes in corneal thickness are not truly representative of diurnal variations in human corneal thickness and, in fact, much greater diurnal variation occurs than the 3.0-4.4% previously reported. (BrJ Ophthalmol 1996;80:1068-1072 Corneal thickness measurements are indicative of the metabolic status of the cornea, as they provide an index of corneal hydration.' Such measurements give valuable information on the physiological status of the cornea and its changes associated with disease,2' trauma,56 and hypoxia.78 The healthy human cornea experiences hypoxia on a daily basis beneath the closed eyelid during sleep.910 The reduction in oxygen levels beneath the closed eyelid is thought to induce anaerobic metabolism, which causes an accumulation of lactate within the stroma which is followed by an osmotic influx of water.7 Other factors could also influence corneal hydration such as the reduced evaporation from the tear film which occurs during the first 2 hours of waking," intraocular pressure which increases rapidly after sleep,'2 and body temperature which changes on a diurnal basis decreasing during night-time sleep and increasing throughout the day.'3 Upon opening the eyelid at waking the corneal thickness is reputed to return rapidly to normal. Thus, corneal thickness changes on a diurnal basis. Such diurnal variations in corneal thickness have been identified in a variety of species, including rabbit,'4 cat,'5 primate,'6 and human.9 17-20It still remains unclear whether overnight changes in human corneal thickness are truly representative of the diurnal variation occurring throughout any 24 hour period or whether the pattern of thickness changes is the same on consecutive days. The aim of this study was to use ultrasonic pachymetry to elucidate the diurnal variation in human corneal thickness in a group of normal healthy human subjects over a 48 hour period. Materials and methods SUBJECTSEight subjects (four male, four female) aged between 10 and 63 years partici...