Computerized topographic analysis of the healing graft after penetrating keratoplasty for keratoconus.

After penetrating keratoplasty, visual rehabilitation can be slow and is largely a function of corneal surface configuration. Computerized topographic analysis allows the detailed study of corneal surface factors that determine the optical function of the graft. We performed a prospective, longitudinal study of eight patients with keratoconus by using computerized topographic analysis to determine the rate and pattern of postoperative surface normalization and stabilization. Study data included Snellen visual acuity, contrast sensitivity function, central keratometry, photokeratoscopy, and computerized topographic analysis. Data were collected preoperatively and at one week, one month, two months, three months, and six months postoperatively. Results demonstrate that the greatest configurational changes both topographically and functionally occur in the first month after keratoplasty. The computer-generated surface asymmetry index and the surface regularity index correlated well with improvement in Snellen visual acuity measurements. Contrast sensitivity function was depressed initially but improved to well above preoperative values by one month postoperatively and paralleled the improvement in the surface indices and visual acuity. The axis of astigmatism stabilized by one month postoperatively. Our data indicate that topographic analysis provides a good indication of the rate and course of optical stabilization during the early healing process after keratoplasty and correlates well with visual function in the otherwise normal eye.

Corneal topography of posterior keratoconus.

Posterior keratoconus is an unusual abnormality of the cornea generally classified as one of the anterior chamber cleavage anomalies. It is characterized clinically by the presence of a circumscribed or generalized corneal thinning with posterior depression of the cornea and is considered distinct from keratoconus. Although patients with posterior keratoconus may have visual complaints clearly related to their abnormal corneas, the surface topography of these corneas has not been studied in detail. Keratometry and photokeratoscopy provide an incomplete picture of the surface geometry of posterior keratoconus. We utilized computer assisted topographic analysis to study the cornea of a patient with posterior keratoconus. The Topographic Modeling System demonstrated that the patient's cornea showed a central steepened "cone" coincident with the area of circumscribed posterior keratoconus as well as paracentral flattening. This report documents the topographic abnormality in this rare disorder.

Herpes simplex dendritic keratitis after keratoplasty.

We treated three patients with herpes simplex dendritic keratitis that occurred between three and 11 months after keratoplasty. The patients had no history of herpetic infection. The eyes of two of the patients were grafted for corneal scarring of undetermined origin. The eye of the third patient was grafted for pseudophakic bullous keratopathy. At the time of onset of dendritic keratitis, all three patients were receiving either maintenance or higher doses of topical corticosteroids. All infections responded to topical antiviral treatment. The findings in these patients illustrate the importance of considering herpes simplex keratitis in the differential diagnosis of all late-onset epithelial defects in the corneal graft, even in the absence of a history of herpes simplex keratitis.

Chronic amphetamine: effects on defensive flight in the rat.

Hooded rats were injected with physiological saline or d-amphetamine sulfate for 13 days on a schedule designed to mimic patterns of abuse: one injection on days 1-11, two injections on day 12, and three injections on day 13; amphetamine dosage for the first three injections was 3.5 mg/kg and for all subsequent injections was 5.0 mg/kg. Amphetamine-treated rats (Amphet) showed a dramatic flight reaction in response to a novel stimulus (mechanical robot) that did not elicit flight from saline control animals. Tested on a slow-moving treadmill that carried them toward the stimulus, Amphet rats accumulated only 15% of the trial time at the front of the apparatus nearest the stimulus and accumulated approximately 75% of the trial time at the extreme rear of the apparatus, farthest from the stimulus. Control tests of Amphet rats in the absence of the stimulus ruled out interpretations in terms of motor behavior. In fact, a major advantage of the present procedure is that animals are able to execute the relatively simple defense response despite the occurrence of motor stereotypy. These results suggest that the defense-response paradigm is suitable for the study of chronic amphetamine and may provide a useful adjunctive to existing models of amphetamine psychosis.

Amphetamine: effects on defensive flight or avoidance in the rat.

Treatment with a moderately high dose of amphetamine caused rats to retreat from a stimulus they would normally approach and explore (mechanical robot or live white rabbit). While saline-treated rats spent approximately equal amounts of time in the area of the apparatus near the stimulus, amphetamine-treated rats spent a high percentage of trial time in the area of the apparatus farthest from the stimulus. The drug effects were dose related (range: 1.75, 3.5 and 7.0 mg/kg) with higher avoidance time at higher doses, and significant linear trends accounting for much of the variance. The highest dose of amphetamine elicited response stereotypy. However, control conditions ruled out the possibility that the present results could be explained by competing motor responses of stereotypy or increased activity. Thus, apart from its actions on motor behavior, amphetamine treatment resulted in rats avoiding or retreating from an otherwise neutral stimulus.

Physostigmine: effects on fear or defense responses in the rat.

Previous research had shown that the anticholinergic drug, scopolamine, decreased innate defensive responses of rats to a live cat or mechanical robot, and that the effects of scopolamine were attributable to actions of the drug on the central nervous system. In the present research, the anticholinesterase, physostigmine, which increases central cholinergic activity, caused an increase in the defense responses of male hooded rats. Physostigmine caused significantly more freezing and significantly more suppression of feeding and suppression of time near the aversive stimulus (ROBOT). Dose-response curves showed a positive, linear relationship between dose (0.025, 0.05, 0.1 and 0.2 mg/kg) of physostigmine and defense responses. The present results could not be attributed to general response suppression since the effects of physostigmine were situation-specific, i.e., the drug had no significant effect on behavior in the non-aversive or NO ROBOT condition. The present results were taken as further evidence of the involvement of cholinergic activity in the mediation of defense responses. The effects of cholinergic and anticholinergic drugs on the observable defense response of freezing were thought to have important implications for the large literature relating these drugs and avoidance responding.

Scopolamine: effects on fear or defense responses in the rat.

In previous research scopolamine reduced fear or defense responses of rats to a cat, and removal of the rats' olfactory bulbs had the same effect. This suggested that scopolamine might have affected defense responses by blocking olfactory perception of the stimulus cat. The present experiments studied this possibility and explored further the effects of scopolamine on defense responses of the hooded rat. In Experiment 1 rats treated with scopolamine were found to be responsive to olfactory cues from a cat. When cat smell, but not a cat, was present in the apparatus, scopolamine-treated rats showed a large and significant suppression of food consumption. In Experiment 2 the effects of scopolamine on defense responses were shown to be generalizable to an inanimate stimulus, mechanical robot. Scopolamine caused significantly less freezing and avoidance and significantly shorter latencies to drink in the presence of the robot. One of the primary findings of the present research is that scopolamine has now been shown to reduce the defensive response of freezing in a variety of stimulus situations. This finding was thought to have important implications for the literature relating anticholinergic drugs and avoidance behavior.

Comparing the effects of scopolamine on operant and aggressive responses in squirrel monkeys.

The anticholinergic drug, scopolamine, causes disinhibition or an increase in responses that an animal normally suppresses. Experiment 1 confirmed this effect in squirrel monkeys. Experiment 2 explored the implications of drug-produced disinhibition on aggressive interactions. In Experiment 1, scopolamine produced increased unreinforced responding on a DRL schedule and increased responding during unreinforced (Time Out) periods. In contrast, the peripheral control drug, methyl scopolamine, caused decreased responding in both situations. In Experiment 2, social rank and drug treatment interacted. When space was restricted so that the opportunity for social interactions was maximized, scopolamine consistently increased aggressiveness in the dominant monkey and decreased aggressiveness in a submissive monkey. When space was increased so that the opportunity for social interactions was minimized, scopolamine caused decreased aggressive responses in all monkeys. Neither the effective dosage nor the drug's effect on the operant task could be easily generalized to aggressive responses.