Exophthalmos in rats

Over a series of experiments, three adult PVG black hooded female rats weighing 240–250 g developed exophthalmos during anesthesia. We use the rats in studies of visual function, and our experiments last >10 h.

Gaseous anesthesia is excellent for the long experimental phase, but can make it difficult to achieve stability during the surgical phase of the experiment. Consequently, we tried a combination of ketamine (Ketaset, 100 mg/ml; 60 mg/kg) and medetomidine (Dormitor, Pfizer UK; 1 mg/ml; 1 mg/kg) given intraperitoneally to induce and maintain a stable platform for surgical preparation of three animals, before the longer (>10 h) experimental data-collection phase of the experiment.

In one rat, exophthalmos (Fig. 1) was noted immediately after anesthesia induction. The photo shown in Figure 1 was taken just before the change in anesthesia, after surgical preparation was complete. Once surgery was complete, we reversed the medetomidine with atipamezole (Antisedan, Pfizer UK; 5 mg/ml) and maintained the animal on halothane in N₂O/O₂. The exophthalmos remained throughout the experiment, which lasted ∼15 h. Recorded neural activity suggested that the visual pathway was intact and functioning normally.

Figure 1: Photograph of a female PVG black hooded rat showing exophthalmos.

The image was taken approximately 30 min after injection of ketamine and medetomidine as an anesthetic combination. The scalp was shaved prior to surgery. The animal was immobile and unresponsive to a paw pinch but retained its corneal reflex.

In a second rat, exophthalmos was noted from anesthesia induction until the reversal of medetomidine with atipamezole, at which time it diminished by ∼50%. The milder exophthalmos persisted for the remainder of the experiment. Zero-power contact lenses (No7 Contact Lens Laboratory, UK) were applied to the rat's eyes after surgical preparation. While the radius of curvature seemed to be correct, we could not cover the exposed surface of the globe, even though these lenses had previously completely covered the exposed globe in other rats. Visual responses were recorded from visual cortical cells and appeared normal. The experiment lasted ∼14 h, and the electrophysiological visual responses remained normal during this time. Heart rate under the ketamine-medetomidine anesthesia was ∼300–320 bpm, rising to 380–400 under halothane, which we considered normal.

The third rat also developed exophthalmos after anesthesia induction. In all cases, we inserted a breathing cannula into the trachea and an intravenous line into the tail vein. We then monitored the animals' ECG continuously. Paralysis was induced by intravenous injection of gallamine (20 mg/kg/h), and thereafter, end tidal CO₂ was continuously monitored and maintained at ∼4%. A craniotomy was performed over the primary visual cortex to allow insertion of data-collecting probes. Medetomidine was reversed with atipamezole before we stabilized the rats on gaseous anesthesia and measured visual system parameters at the single-cell level during the long phase of the experiment. Each experiment was terminated when we euthanized the test rat with pentobarbitone sodium (Euthatal, Merial Animal Health Limited) overdose (200 mg/ml intravenous).

We noticed exophthalmos almost immediately after anesthesia induction with medetomidine-ketamine. The globe protruded ∼2 mm or more beyond normal (Fig. 1). A 'blink response' remained, but the eyelids were unable to close over the exposed globe. Infrequent but very noticeable eye 'movements' occurred, in which the globe was briefly retracted to near normal, then returned to the exposed position. What do you think is the cause of the exophthalmos? Is it a problem that could compromise the research? How would you deal with it?

What's your diagnosis?