Juan Ding, OD, PhD

The flu season is upon us now. Many people are getting sick, coughing, sneezing, having a fever, and sometimes developing pink eyes, also known as infectious conjunctivitis. There are also people who develop pink eyes without any other cold symptoms. Pink eyes are miserable, with redness, pain, discharge and sometimes blurry vision. They look awful, you cannot go to work as people will ask questions, and rightfully so as infectious conjunctivitis is quite contagious.

So how can you get well quickly? Patients often go to doctors asking for drops that will ease the pain and make them look normal again.

What can eye doctors give patients to make their pink eyes better?

Many primary care doctors will give patients antibiotic eye drops. Eye doctors, however, are trained not to do that automatically. You see, not all pink eyes will respond to antibiotic drops. In fact, we are taught that most pink eyes are caused by viral infections, which will not respond to antibiotics, and using antibiotics in this situation will contribute to antibiotic resistance.

So how to tell bacterial from viral infections? It’s not possible for a patient to do this. It’s actually difficult even for eye doctors. There are certain characteristics that are classical for viral vs bacterial, but many features are overlapping between the two. The only accurate way is to culture or test specifically for the pathogen. Unfortunately, this is almost never done in any eye doctors’ offices. I can imagine the reason to be related to cost, and most pink eyes get better even without treatment anyways.

There is a product similar to a quick strep throat swab test, that checks if the pink eye is from adenoviral infection, which is considered to be the most common virus to cause pink eyes. If your eye swab tests positive for adenovirus, then the pink eye is confirmed to be from this virus, and no treatment is going to be needed, as this virus does not respond to antibiotic drops, nor to the antiviral drops currently available. So just use artificial tears and cold compress to make yourself a bit comfortable while waiting it out.

However, even though the product is there, the adenoviral testing is still not widely used in most offices. Cost being one reason, and the other reason is that it tests for only one thing. If you test negative for adenovirus, then you don’t know whether it’s another virus or it is a bacterium, or fungus, so that does not help with the treatment.

So now there is a new study [1] that checked for any possible pathogen for pink eyes. They collected eye and nose swabs of 52 adult patients with pink eyes from 4 sites in the US and 1 site in Israel, and did DNA sequencing in these samples and compared the sequence to all the currently known DNA sequences of microorganisms. This way, anything that caused the pink eye is being looked at, not just adenovirus. The results are interesting.

First, they did find that most of the infections are from virus rather than bacteria. 54% were from viruses and only 8% from bacteria. 35% they were not able to identify any pathogen (could be due to some of the patients already started on antibiotic drops, or technical difficulties, or the presumed diagnosis of infectious conjunctivitis is just wrong). And the rest (3%) are from fungus.

This is great confirmation that most pink eyes are viral, but I am disappointed that they included 33% of patients who started antibiotics before sampling, and you have 35% samples tested negative for any pathogen. This looks suspicious, what if these are rightly diagnosed as bacterial conjunctivitis and treated successfully before sample collection, hence the negative hit in pathogen database. If that’s the case, then the bacterial etiology is not as infrequent as we think. They should have analyzed the 35% negative results in depth, especially cross referencing to those who took antibiotics beforehand. I’m surprised this slipped through the reviewers as well as authors.

Still, their findings are useful and eye opening as they debunk certain myths around infectious conjunctivitis.

We are taught that one way to differentiate bacterial vs viral is that bacterial infection causes mucopurulent discharge vs virus causes watery discharge. But this study finds that while all the bacterial conjunctivitis produced mucopurulent discharge, 17 viral conjunctivitis patients also presented with mucopurulent discharge. So out of the 28 with viral etiology, that is 61% of all viral conjunctivitis show mucopurulent discharge. This tells us that if a person has watery discharge, it’s most likely not due to bacteria, but if they have mucous discharge, you cannot say for sure that they have bacterial infections. This also implies that bacterial conjunctivitis is probably over-diagnosed, as doctors may use the texture of the discharge as a criterion.

Another myth is that itchy eyes equal allergies, and infectious conjunctivitis produce pain or discomfort, rather than itchiness. Their study found that 64% of patients report eye itchiness. So this is an overlapping symptom of infection with allergy. You cannot conclude a conjunctivitis is due to allergy just because patients feel itchiness.

Third myth is that viral rather than bacterial conjunctivitis is associated with swollen lymph nodes. In the study, only 4 out of the total 52 cases show preauricular lymphadenopathy (PAN). This is something I see in clinic frequently. Most viral conjunctivitis does not present with PAN.

We are taught that most viral conjunctivitis is caused by adenovirus. In this study, 13 of 28 viral cases (46%) were indeed due to adenovirus. The other viruses identified included: 3 with human coronavirus 229E, 1 with SARS-CoV-2, 3 cases of herpes simplex virus type 1 (HSV-1), 2 cases of varicella-zoster virus (VZV), and 2 cases of Epstein-Barr virus, 1 case was positive for human metapneumovirus.

Both human coronavirus 229E and human metapneumovirus commonly cause cold and sometimes pneumonia. The same with adenovirus, which seems to have a predilection for conjunctival infection, while also causing common cold and sometimes pneumonia. There is no treatment for these viruses, and their conjunctival infections typically are self-limited.

Therefore, in viral conjunctivitis, no antibiotic eye drops should be given.

HSV and VZV can cause pink eyes as well. Antibiotic eye drops will not work on these herpes viruses so should not be given. But unlike other viral causes, there are anti-viral medications that can be used to treat HSV and VZV. Without other concomitant presentations, such as findings in the cornea and on eyelid skin, it can be difficult to differentiate HSV or VZV from other viral causes. Given HSV and VZV only represent a small percentage of the viral conjunctivitis, it may not be worthwhile treating every pink eye with antivirals.

Therefore, we typically don’t treat pink eye with antivirals if there is no involvement of the cornea or other tissue of the eye.

How about bacteria?

Bacteria were identified in 4 patients (8%), including Haemophilus influenzae, Fusobacterium nucleatum, and Streptococcus pneumoniae.

Haemophilus influenzae and Streptococcus pneumoniae are known human pathogens to cause respiratory tract infections, as well as more invasive systemic infections. When these cause conjunctivitis, most antibiotic eye drops will successfully treat the disease.

Fusobacterium nucleatum is actually a commensal bacterial living in the oral cavity and rarely found elsewhere in the body. However, it can cause oral infections, GI disorders, problems with pregnancy, rheumatoid arthritis and Alzheimer’s disease, among many [2]. It is a Gram-negative, anaerobic bacterium, so most of the antibiotic eye drops should take care of it.

So yes, if we are certain the pink eye is caused by bacteria, then antibiotic eye drops are warranted.

Fungus was identified in 2 patients (4%), Rhizopus oryzae, which is a mold found in soil and food, an opportunistic pathogen of humans causing mucormycosis. Fortunately this is quite rare for pink eyes, because the treatment would have been an anti-fungal eye drop.

So in summary, most of pink eyes in adults are caused by viruses, which are often self-limited and non-responsive to antibiotics (or even antivirals that we currently have), so it is wise not to jump into antibiotics automatically. However, it is not easy to differentiate bacterial vs viral causes, and new research further made this point. Maybe one day there will be a diagnostic panel that detects multiple viruses and bacteria at the same time quickly to help doctors with more accurate diagnosis and proper treatment. Until then, we do what we do most of the time, to comfort and to let the body heal with time.

 References

[1] Tsui E, Sella R, Tham V, et al. Pathogen Surveillance for Acute Infectious Conjunctivitis. JAMA Ophthalmol. Published online November 02, 2023. doi:10.1001/jamaophthalmol.2023.4785. https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2811380?guestAccessKey=1de9f48e-f5f4-47dc-8590-e40f7273c081&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jamaophthalmology&utm_content=olf&utm_term=110223&adv=null

[2] Han YW. Fusobacterium nucleatum: a commensal-turned pathogen. Curr Opin Microbiol. 2015 Feb;23:141-7. doi: 10.1016/j.mib.2014.11.013. Epub 2015 Jan 8. PMID: 25576662; PMCID: PMC4323942.