Managing Glaucoma with a Holistic View

Why care and counselling should consider systemic diseases and medications. Cheryl Guttman Krader reports

Patients with glaucoma should be asked about existing systemic diseases and medications because certain medical conditions and drugs can be associated with increased IOP and risk for glaucoma development and progression, advised Gerhard Garhöfer MD.

“It makes sense to look at our patients as a whole. We should not only concentrate on the eye,” Dr Garhöfer said.

Learning about a patient’s blood pressure (BP) and existing treatment for systemic hypertension is important, especially considering almost one-third of the world’s adult population suffers from systemic hypertension.i

“I am pretty sure that all of you who see glaucoma patients regularly have been asked whether having systemic hypertension affects glaucoma,” Dr Garhöfer observed.

The answer to the question is both yes and no. From a statistical point of view, there is an association between BP and IOP. However, from a clinical point of view, the association is “very, very” weak, and is probably not clinically relevant for most patients, Dr Garhöfer said.

Findings from a meta-analysis showed an increased risk of primary open-angle glaucoma (POAG) among patients with hypertension and a positive association between BP and IOP. The average increase in IOP with a 10 mmHg increase in systolic BP or a 5 mmHg increase in diastolic BP was minimal.

“A 40 mmHg increase in systolic BP would translate to just a 1 mmHg increase in IOP,” Dr Garhöfer explained.

Discussing the potential association between ocular perfusion pressure (OPP) and glaucoma risk, Dr Garhöfer noted available evidence also establishes an association between low diastolic OPP, which can occur in subjects treated for systemic hypertension, and increased glaucoma risk. Yet, doubts have been raised regarding whether OPP is the right measure for assessing glaucoma risk considering it cannot be measured directly and instead is a calculated value based on mean arterial pressure and IOP.

“So, OPP is not independent of IOP, which raises the question of the relative contributions of IOP and systemic BP to OPP. A lot of people believe we should look at these two factors differently,” Dr Garhöfer noted.

“As a take-home message, however, it is clear that patients with a very high IOP and a low BP are at considerable increased risk of glaucoma.”

Ophthalmologists should also be aware that patients treated aggressively for systemic hypertension to manage cardiovascular risk may suffer from nocturnal dips in BP that have been shown to increase risk of glaucoma progression. According to the findings of a meta-analysis focusing on this issue, a nocturnal decrease of more than 10% in systolic or diastolic BP confers a significant risk for progressive visual field loss.ii

“It makes sense to look at our patients as a whole. We should not only concentrate on the eye.”

“We should be particularly careful and obtain 24-hour BP measurements in these patients,” Dr Garhöfer suggested.

OTHER SYSTEMIC ASSOCIATIONS Multiple epidemiological studies show a significant association between type 2 diabetes and higher risk of OAG but have yet to establish a biological explanation for the connection. A slight increase in IOP also found in patients with diabetes does not fully account for the increased risk. A current theory proposes accumulation of advanced glycation end products may lead to retinal ganglion cell apoptosis, Dr Garhöfer said.

A variety of systemic inflammatory and autoimmune conditions can also involve ocular structures and lead to increased IOP. The list includes sarcoidosis, Behçet’s disease, HLA-B27-related uveitis, juvenile idiopathic arthritis-associated uveitis, and VogtKoyanagi-Harada syndrome.

In addition, there is a striking association between increased body mass index (BMI) and risk for increased IOP.

“It is not easy to treat increased BMI, but it is still a good thing to talk to patients about,” Dr Garhöfer said.

DRUG EFFECTS Considering glaucoma prevalence increases with age, clinicians should recognise there is also an age-related increase in systemic medication use and certain medications increase IOP.

“Two-thirds of adults aged 48 to 64 years and 90% aged 65 years and older take five or more medications,” Dr Garhöfer said.

Uncovering use of an oral beta-blocker is relevant when deciding on topical IOP-lowering therapy because a topical beta-blocker may be less effective in patients on a systemic betablocker. Concomitant use of the two medications also increases the risk for adverse beta-blocker effects.

Corticosteroids, however, are the classic drug culprit for raising IOP. An increase in IOP occurs in 30% of patients using a corticosteroid, and approximately 5% of individuals are “high responders”, meaning their IOP will increase significantly by greater than 15 mmHg and to more than 31 mmHg. Increased IOP can occur regardless of the administration route and is a concern considering the frequency of corticosteroid use.

“An estimated 7% to 10% of adults in Europe are on a corticosteroid, which is quite a high number.”

Dr Garhöfer presented at the Glaucoma Day session of the 40th ESCRS Congress in Milan.

i Mills KT, Stefanescu A, He J. “The global epidemiology of hypertension”. Nat Rev Nephrol. 2020 Apr; 16(4): 223–237. doi: 10.1038/s41581-019-02442. Epub 2020 Feb 5. PMID: 32024986; PMCID: PMC7998524. ii Bowe A, Grünig M, Schubert J, Demir M, Hoffmann V, Kütting F, Pelc

A, Steffen HM. “Circadian Variation in Arterial Blood Pressure and

Glaucomatous Optic Neuropathy--A Systematic Review and Meta-

Analysis”. Am J Hypertens. 2015 Sep; 28(9): 1077–82. doi: 10.1093/ajh/ hpv016. Epub 2015 Mar 11. PMID: 25767134.

Gerhard Garhöfer MD, Section Head, Department of Ophthalmo-Pharmacology, Medical University of Vienna, Austria. gerhard.garhoefer@meduniwien.ac.at