In vivo bulbar conjunctival structures study results in
Cross-sectional structures of the bulbar conjunctival tissue can be accurately measured
Glaucoma is a chronic disease. It is a life sentence. With advances in glaucoma care such as minimally invasive glaucoma surgeries (MIGS), patients are increasingly becoming less reliant on topical therapy. However, a great many patients with glaucoma will be reliant on at least one anti-glaucoma drop for a period of time.
Prostaglandin analogs are commonly viewed as first-line medical therapies for glaucoma. They are known to be well-tolerated systemically, tend to work well at lowering intraocular pressure (IOP), and patients tend to have fewer compliance problems with them because the drops are dosed only once a day. Of course, ODs know they can make patient eyes red. That side effect occurs by definition, as these medications are analogs of molecules naturally occurring in the inflammatory cascade of immune systems. It is expected for such a molecule to cause a bit of inflammation.
Think about anterior uveitis patients who tend to have lower IOP. These patients happen to have inflammatory molecules flowing through the currents of their anterior chambers.
Study findings
A paper recently published in BMC Ophthalmology described a noninvasive method of qualifying and quantifying changes to the conjunctival structures of patients using topical anti-glaucoma medications: anterior segment optical coherence tomography (AS-OCT).1
This cross-sectional study looked at 328 eyes in 199 patients, with 116 females and 83 males. The mean age was 72.1 years, and the median number of anti-glaucoma drops used was 0.79 (with a range of 0 to 4). The mean duration of therapy was 7.5 months. Patients with a history of ocular surgery or ocular trauma were excluded, as were patients using any drops besides those for glaucoma and patients with dry eye disease.
The arm of the study with no glaucoma and no glaucoma therapy was comprised of 236 eyes of 138 patients. Some 101 eyes of 60 patients had glaucoma and were on anti-glaucoma drops. One eye of 1 patient had glaucoma but was on no drops.
As for types of glaucoma in this study population, the most common was primary open-angle glaucoma (52 eyes of 30 patients) with normal-tension glaucoma next (17 eyes of 11 patients). Some 16 eyes of 12 patients had exfoliative glaucoma, and a few patients had neovascular glaucoma, primary angle closure glaucoma, or another secondary glaucoma.
Study investigators obtained AS-OCT images of the bulbar conjunctivae of patients using a CASIA SS-1000 (Tomey). Through these images, they identified 3 specific conjunctival layers: the conjunctival epithelium, conjunctival stroma, and Tenon’s capsule.
Results showed patients who used prostaglandin analogs as monotherapy, or combination drops containing prostaglandin analogs, tended to have lower preservation rates in their bulbar conjunctiva, specifically at the border between the conjunctival stroma and Tenon’s capsule and the border between Tenon’s capsule and sclera.
Prostaglandin analogs are known to induce conjunctival inflammation even in the short durations of use.2
Of note, the use of α2-receptor agonist (such as brimonidine) was associated with higher preservation rates of these aforementioned conjunctival borders. The authors note that a reduced number of inflammatory cells present in the conjunctivae of patients using α2-receptor agonists as opposed to beta blockers or prostaglandin analogs may be the cause for this finding.3
They also note the preservative in brimonidine may also play a role. Several study limitations are outlined. It is unknown whether these findings would play a role in the success or failure of anterior segment surgical procedures, such as trabeculectomies.
They also note that, due to the cross-sectional design of this study, it is unknown whether or not these findings are reversible. Longitudinal studies with large cohorts are needed to determine these details.
Of course, there is also the point that SD-OCT studies are not histological samples, although it is desirable that they are noninvasive. They are not photographs of various tissues of the eye. They are, rather, differences in optical reflectivity.
Deductions
Did reading and digesting this study change how I treat my glaucoma patients? No. The majority of my glaucoma patients are currently on prostaglandin analog monotherapy, and I still consider, for practical purposes, a prostaglandin analog dosed once a day and a combination drop dosed twice a day as maximum medical therapy.
However, I will say that this is an intriguing study with potential implications.
Is it possible that certain anterior segment surgeries fail due to some of these conjunctival findings? Again, longitudinal studies with large cohorts are needed to confirm or deny this notion. However, AS-OCT studies before surgical procedures may play a role in determining who is a better candidate for each procedure.
Much of this is conceptual in nature, yet it is of benefit to conceptualize more uses for such a quick and noninvasive diagnostic test as AS-OCT. There is likely much use of optical coherence tomography science that we have yet to elicit.
References
1. Gozawa M. Takamura Y. Iwasaki K. Arimura S. Inatani M. Conjunctival structure of glaucomatous eyes treated with anti-glaucoma eye drops: a cross-sectional study using anterior segment optical coherence tomography. BMC Ophthalmol. 2020;20(1):244.
2. Rodrigues Mde L, Felipe Crosta DP, Soares CP, Deghaide NH, Duarte R, et al. Immunohistochemical expression of HLADR in the conjunctiva of patients under topical prostaglandin analogs treatment. J Glaucoma. 2009 Mar; 18(3):197-200.
3. Noecker RJ, Herrygers LA, Anwaruddin R. Corneal and conjunctival changes caused by commonly used glaucoma medications. Cornea. 2004 Jul; 23(5):490-6.
