About a year ago, I wrote a review of Ocu-GLO, an oral supplement marketed for a variety of purposes:
Ocu-GLO Rx™ is needed when your dog is showing any of the following signs:
– Diminished vision at night or in dim conditions – Diminished vision at all times – Cloudy appearance to eyes – Pupils that do not constrict – Obvious cataracts Or… -Your dog is generally healthy, but you want him or her to be placed on an excellent lifetime antioxidant supplement to help support and enhance ocular health and also general health.
We (Drs. Carmen Colitz and Terri McCalla) are also dispensing Ocu-GLO Rx™ for patients predisposed to primary glaucoma (having lost their first eye to glaucoma) and that already have glaucoma; for Golden Retrievers with pigmentary uveitis (also called “Golden Retriever Uveitis” or GRU); for diabetic dogs in which cataracts are immature or have not yet formed; for dogs with senile retinal degeneration; for dogs post-cataract surgery to help reduce the incidence of PCO and ACO (Posterior Capsular Opacity and Anterior Capsular Opacity) and for any dogs for which owners want to provide the best nutritional support for their pet’s eyes.
At the time, I concluded that the theoretical premise behind the product and the specific ingredients included was plausible but supported only by weak evidence, and there was little direct clinical research in humans, and virtually none in dogs, showing actual benefits. Therefore, no firm conclusion about the safety and efficacy of the product was possible.
I also noted that:
Unlike the marketing for many supplements pitched to pet owners, the claims made by this company are pretty measured and reasonable in light of the limited available evidence…Hopefully, the ophthalmologists behind the product will pursue appropriate research efforts to determine if, in fact, the product has the benefits they suspect and what, if any, risks are associated with its use.
I was pleased, therefore, to see a clinical trial investigating Ocu-GLO published this month which adds to the evidence regarding this product.
Williams, D. Fitchie, A. Colitz, C. An Oral Antioxidant Formulation Delaying and Potentially Reversing Canine Diabetic Cataract: A Placebo-controlled Double-masked Pilot Study. Int J Diabetes Clin Res 2015, 2:1
This trial targeted a specific disease, cataracts developed by diabetic dogs. The process of cataract formation in diabetics is well understood, and there is reason to expect at least some of the ingredients in Ocu-GLO might influence this process, so again there is a plausible potential mechanism here that is consistent with established science.
The study involved giving either the supplement or a control containing antioxidant vitamins but not several of the other ingredients in Ocu-GLO, to 15 dogs each and monitoring them for changes in their lenses that would indicate cataract formation. It was not considered ethical to allow actual cataract development, so once such signs appeared, the treatment was identified and dogs who had been getting the control vitamins were switched to the supplement.
The results were quite impressive.
Mean time without change in lens opacification at the time of writing was 278±184 days with Ocu-GLO Rx™ and 77 ± 40 days in the placebo group. Median duration without lens change was 261 and 84 days, respectively, this difference being statistically significant at p=0.0003.
Twelve of the 15 dogs (80%) taking the placebo developed significant lens changes while on the study protocol. Five of 15 dogs (33%) taking Ocu-GLO Rx™ developed significant cataract, in three of these animals Ocu-GLO Rx™ was not being given as directed…
These differences between the groups is not only statistically significant but, far more important, they are clinically relevant. While the supplement did not absolutely prevent lens changes in treated dogs, it appeared to dramatically delay these changes. In one subject who was switched from the control supplement to the test product, it appeared that the product even reversed changes that had already begun.
Like all research, there are flaws and limitations to this study which require some skepticism about even such dramatic results. To begin with, several key methodological factors were not mentioned in the published report. This is unfortunately extremely common in veterinary research. However, I contacted Dr. Williams, the lead author, and he was kind enough to answer a few questions and provide at least some of this missing information.
There is no mention in the paper of how the subjects were assigned to the two groups. Random assignment, and a process which prevent anyone from intentionally or unconsciously influencing the selection and assignment of patients, is a critical component to reducing bias and error in clinical trials. According to Dr. Williams, the subjects were individually randomized to the two groups. It is not entirely clear, though, how this process was protected from being unintentionally influenced by study personnel or how the exact balance in number between the groups was achieved.
Blinding of investigators and owners to the treatment assignment is another critical element of an effective clinical trial. It appears that investigators were effectively blinded to the treatment each patient received. This is especially important because the outcome being measured was subjective and not very precisely defined as “significant progression of lens opacity, as documented photographically.” It is not clear if the owners could distinguish the two treatments, but this would be less likely to have a significant impact on the results since owners were not involved in assessing the outcome.
A number of other potential limitations exist in this study, including minimal comparison of the two groups before treatment to ensure there were no relevant differences and a small number of subjects, but in general the design and execution seem quite good.
One of the authors, Dr. Colitz, is affiliated with the company marketing Ocu-GLO. This raises the potential of unconscious or overt bias, but this is likely mitigated by the blinding, randomization, and other typical bias-control aspects of the study. Dr. Williams also indicated that there was no financial support of the study from the manufacturer, reducing the risk of any funding bias.
The issue of adverse effects was not specifically addressed in the published report. The company has previously indicated that some unpublished data exist demonstrating the product is safe, and there is no specific evidence to suggest any risk, though unintended effects with long-term use or in particular patients cannot be completely ruled out. With the limited evidence currently available, there seems to be little risk to the use of this product.
I have previously discussed the Decline Effect, which is a well-recognized phenomenon in which small, early studies of a scientific hypothesis give dramatic results which diminish, and sometimes disappear entirely, in subsequent research with better control for bias, confounding, and other sources of error. So it is important to remember that no single study ever definitively proves or disproves a scientific hypothesis. As the researchers themselves acknowledge, further research is not only desirable but necessary to allow confidence in these findings and this treatment.
This is a small but well-executed clinical trial with a large, clinically relevant difference in the progression of changes in the lens clarity of dogs with diabetes treated with Ocu-GLO compared with a control supplement. The trial is not perfect, of course, and no single trial should ever be viewed as definitive. And this study applies only to the issue of using this supplement to slow the development of cataracts in diabetic dogs. It does not provide good evidence that the supplement can completely prevent or cure cataracts or that it is effective for other uses.
As always in veterinary medicine, however, we must make decisions on the basis of the imperfect evidence we have, while still pursuing more and better evidence. Though the evidence is still limited at this point, I believe it is good enough to recommend the use of this supplement for cataract prevention in diabetic dogs.