Effects of Oral Macrocyclic Lactone Heartworm Preventatives on Retinal Function and Chromatic Pupillary Light Reflex in Healthy Companion Dogs

Abstract

Objective: Determine the effect of oral macrocyclic lactone heartworm-preventative medications on retinal function and chromatic pupillary light reflex (cPLR) in healthy dogs.

Animals studied: Cross-sectional retrospective: 60 dogs (n = 33 females) with heartworm medication administration status and electroretinogram (ERG) data available. Prospective clinical study: 25 dogs (n = 10 females) had ERG performed, 18 of which had cPLR performed.

Procedures: Retrospective: ERG amplitudes/peak times were compared between dogs that had or had not received oral heartworm preventatives. Bivariate and multiple variable linear regression models were used to evaluate relationships between ERG testing and heartworm preventive administration status, age, and sex.

Prospective: ERG and cPLR testing were performed at a baseline visit (minimum 14 days since last preventative administration), and a second visit where ERG/cPLR testing was performed 4 h after oral preventative administration. Mixed effects models and Mann-Whitney U statistics were performed.

Results: Retrospective: There was no association between heartworm preventive administration status and ERG amplitudes or peak times (all p-values > 0.12).

Prospective: Heartworm preventative had no effect on light- and dark-adapted ERG amplitudes or peak times (all p-values > 0.56). Similarly, there was no effect on baseline pupil size (p = 0.83), nor on cPLR (p = 0.32).

Conclusion: No significant effects of oral macrocyclic lactones on retinal/cPLR function at preventative doses were identified. While small effects on retinal/cPLR function cannot be completely ruled out, it remains unlikely that these medications cause clinically significant visual deficits at prescribed doses, and proven antiparasitic benefits likely far outweigh small potential ophthalmic risks of administration.

Keywords: SARDS; electroretinography; ivermectin; milbemycin oxime; moxidectin; sudden acquired retinal degeneration syndrome.

FIGURE 1

Retrospective study: ERG amplitudes in dogs that did or did not receive heartworm‐preventative medication. Data are presented for a‐wave amplitude (A), b‐wave amplitude (B), where data are presented for dogs that either received heartworm preventative (HWP) or did not (no HWP). Graphs (C) and (D) demonstrate the same data, separated by heartworm medication type. For (A) and (B): N = 18 no HWP, n = 42 HWP, for (C) and (D): N = 18 no HWP, n = 13 milbemycin oxime, n = 5 moxidectin, n = 24 ivermectin.

FIGURE 2

Prospective study: Example ERG waveforms from the baseline (BL) and heartworm (HW) visit. Traces from the same dog are shown (84‐month‐old male neutered Greyhound) that received ivermectin as the active heartworm‐preventative ingredient. Black lines represent BL, gray lines HW.

FIGURE 3

Prospective study: Effect of heartworm medication on ERG parameters. Light‐ and dark‐adapted ERG raw values are shown at baseline (BL) and heartworm (HW) visits (A–D). Data are presented for a‐wave amplitude (A), b‐wave amplitude (B), a‐wave peak time (C), and b‐wave peak time (D). The percentage change in ERG b‐wave amplitude is shown for each heartworm medication drug class (E). Mixed effects model statistics are shown below each graph, showing p‐values for the effect of medication administration (A–D) or medication class (E), stimulus intensity and the interaction between these two terms. In (A–D), black dots represent BL, gray dots HW, the red and blue dots represent the three dogs with the greatest reduction in red light PLR at the HW visit. In (E), black dots represent ivermectin, red dots represent moxidectin, blue dots represent milbemycin oxime.

FIGURE 4

Prospective study: Chromatic pupillary light reflexes with heartworm medication administration. (A) Representative images are shown for both visits from the same dog (73‐month‐old male neutered Labrador Retriever administered moxidectin). This dog had a 24% light‐induced change in constriction at baseline and 14% light‐induced change in constriction at the heartworm visit (red light) and a 39% light‐induced change in constriction at baseline and 31% light‐induced change in constriction at the heartworm visit (blue light). (B) Baseline pupil size (percentage dilated) for both visits. Mann–Whitney U test. Black dogs represent BL, gray dots HW. (C) Data for all dogs for change in constriction percentage at baseline (BL) and heartworm (HW) visits are shown. Mixed effects model statistics are shown below each graph, showing p‐values for the effect of medication administration, stimulus color, and the interaction between these two terms. (D) The difference in pupil percentage constriction with light administration between HW and BL visits (HW minus BL) for red and blue lights. p‐value represents Mann–Whitney test comparing red and blue lights. Black dots represent BL, gray dots HW, red and blue dots represent the three dogs with the greatest reduction in red light PLR at the HW visit.