A steroid responder is someone whose eye pressure climbs abnormally high when they use corticosteroid medications. The term dates to the early 1960s, when researchers Armaly and Becker independently showed that people fell into distinct groups based on how much their intraocular pressure (IOP) rose during weeks of topical steroid treatment: some showed almost no change, others a moderate bump, and a smaller group experienced a dramatic spike. That susceptibility is largely invisible until steroids are actually used, which is what makes identification tricky and monitoring so important.
Where the Term Comes From
The connection between corticosteroids and rising eye pressure was first reported in 1950, when long-term systemic steroid use was shown to push IOP upward. But it was a cluster of studies in 1962 and 1963 that defined steroid responsiveness as a measurable, graded trait. Bernstein and Schwartz found that patients on long-term oral steroids had consistently higher IOP than normal individuals. Then Becker and Mills noticed something revealing: when they applied steroid drops to the eyes of glaucoma patients, those patients’ pressures climbed far more than in healthy volunteers. Normal subjects, meanwhile, split into two distinct subgroups, some with a moderate rise and others with barely any rise at all.
Armaly confirmed the pattern and added another layer, noting that older eyes responded more than younger ones. Together, Armaly and Becker refined the classification into three tiers: high responders (IOP increase greater than 15 mmHg), moderate responders (6 to 15 mmHg), and low responders (less than 6 mmHg). People predisposed to these pressure elevations became known as “steroid responders,” a label the field still uses today.1PubMed Central. Steroid-Induced Ocular Hypertension/Glaucoma: Focus on Pharmacogenomics and Implications for Precision Medicine
What Happens Inside the Eye
To understand why steroids raise eye pressure, you need to know that the eye constantly produces fluid (called aqueous humor) and drains it through a tissue called the trabecular meshwork. Think of it like a drain filter. In steroid responders, corticosteroids cause changes to this meshwork that make it harder for fluid to pass through. The fluid backs up, and pressure rises.
Research has shown that glucocorticoids have wide-ranging effects on trabecular meshwork cells. They alter gene expression, change the structural scaffolding of cells, and promote buildup of material in the spaces around cells, all of which can clog the drainage pathway.2PubMed. The role of steroids in outflow resistance The clinical picture that results looks a lot like primary open-angle glaucoma, the most common form of glaucoma. The key difference is that steroid-induced pressure elevation is usually reversible once the steroid is stopped, whereas primary open-angle glaucoma is a chronic, progressive condition. If steroid-induced high pressure goes unnoticed and untreated for a long time, though, it can cause permanent optic nerve damage just as any other form of glaucoma would.
How Steroid Responders Are Identified
There is no blood test or genetic screen that reliably flags someone as a steroid responder before they begin treatment. Identification is almost entirely clinical: you use the steroid, and your eye doctor monitors your pressure at regular intervals to see if it rises beyond what is expected.
A typical monitoring protocol involves checking IOP at baseline before starting the steroid, then rechecking at weekly or biweekly intervals. In one formal study design, baseline measurements were taken on day zero, with follow-up exams on days 7, 14, 21, 28, 35, and 42, continuing for six weeks or until the pressure rose by 10 mmHg or more above baseline.3PubMed. Identification of high intraocular pressure responders to topical ophthalmic corticosteroids In everyday clinical practice, the monitoring schedule is usually less rigid but follows the same logic: repeated pressure checks during the first several weeks of steroid use.
Increased IOP from steroid drops typically develops during the first few weeks of use.4PubMed Central. A very early steroid responder after cataract surgery: a case report But the timeline can vary. Some patients experience a very early spike within the first day or two, which catches clinicians off guard because steroid response is not generally considered a cause of immediate postoperative pressure elevation. Other patients may not show an increase for months, particularly with systemic or injected steroids that linger in the eye for longer periods.
Who Is at Higher Risk
Whether or not someone responds to steroids depends on the specific drug, the dose, how often it is used, and the individual’s own responsiveness.5PubMed. Corticosteroids and glaucoma risk But certain groups are more likely to be steroid responders than others.
People who already have primary open-angle glaucoma are at the top of the risk list. The early studies by Becker, Mills, and Armaly showed that glaucoma patients experienced far greater IOP rises than people without the disease. Family members of glaucoma patients also appear to be at higher risk, suggesting a shared underlying susceptibility.
Age and eye anatomy also play a role. A study of cataract surgery patients found that younger patients with high myopia (severe nearsightedness) had a higher risk for a postoperative steroid response and may need more frequent pressure monitoring or alternative anti-inflammatory medications.6PubMed. Risk factors for steroid response among cataract patients This is somewhat counterintuitive: the original 1960s research found older eyes to be more responsive, but in the context of post-surgical steroid drops, younger patients with elongated eyeballs seem particularly vulnerable.
Pre-existing ocular hypertension or glaucoma is another powerful predictor. In a study of patients receiving an intravitreal dexamethasone implant (a slow-release steroid injected into the eye), half of patients who already had glaucoma or elevated pressures before the injection went on to develop sustained pressure elevation afterward, compared with a much lower rate in patients without that history.7PubMed Central. Ocular hypertension and its predictor after a single Ozurdex implant: One-year follow-up in Asian Indian eyes
The Genetics Question
Given that steroid responsiveness runs in families and clusters with glaucoma, researchers have spent decades looking for genetic markers that could predict it. So far, the search has been frustrating. Multiple studies testing common genetic variants associated with the glucocorticoid receptor itself have come up empty. One study examined variants in five genes connected to glucocorticoid receptor function and found no significant differences between steroid responders, glaucoma patients, and normal controls.8PubMed Central. Assessment of SNPs associated with the human glucocorticoid receptor in primary open-angle glaucoma and steroid responders A separate study looked at three glucocorticoid receptor variants and their relationship to pressure elevation after intravitreal steroid injections, again finding no statistically significant correlations.9PubMed. Glucocorticoid receptor polymorphisms and intraocular pressure response to intravitreal triamcinolone acetonide
One broader effort using a genome-wide approach did identify several genetic markers that correlated with steroid-induced pressure elevation in a Caucasian population, but when these same markers were tested in an Indian population, only one showed any association, and even that varied depending on the specific steroid used.10PubMed Central. Assessment of single nucleotide polymorphisms associated with steroid-induced ocular hypertension The genetic architecture of steroid responsiveness appears to be complex and probably involves many genes with small individual effects, making a simple predictive test unlikely in the near future. For now, the practical reality is that you cannot know who will respond until they are monitored on the drug.
Route of Administration Matters
Not all steroid treatments carry the same risk. Eye drops are the most common culprit because the drug is delivered directly to the tissues involved. Potent drops like prednisolone acetate and dexamethasone are well known to raise IOP in susceptible individuals. Injections placed inside the eye, particularly long-acting implants like the dexamethasone intravitreal implant (commonly known by the brand name Ozurdex), pose a particular challenge because the steroid sits in the eye for months and cannot simply be “stopped” the way a daily eye drop can.
In a large series of intravitreal dexamethasone implant injections, ocular hypertension occurred after roughly a quarter to a third of injections across different studies. One study of 1,000 injections reported a 28.5% rate of elevated pressure, with about a third of affected eyes requiring pressure-lowering drops.11Retina. Safety of Intravitreal Dexamethasone Implant (Ozurdex) Another found a 23.3% rate after 172 injections, with about 10% needing drops and a small number requiring laser or surgical procedures.12PubMed Central. Management of ocular hypertension following intravitreal dexamethasone implant (ozurdex) The episodes were generally transient and manageable, but the inability to remove the implant once it is in the eye makes careful patient selection and follow-up essential.
Systemic steroids, such as oral prednisone, can also raise eye pressure, though typically less dramatically than direct ocular administration. Inhaled steroids and skin creams occasionally cause pressure elevation too, particularly if used heavily near the eyes. The general principle is that the closer the drug is to the trabecular meshwork, the greater the risk.
Children Are Especially Vulnerable
Children deserve separate mention because they appear to be more susceptible to steroid-induced pressure rises and are at the same time the least likely to report symptoms or receive proper monitoring. One case series documented devastating outcomes in children who had been given steroid eye drops for allergic eye conditions without adequate follow-up. By the time these children were seen by a specialist, they already had advanced optic nerve damage and high pressures.13PubMed Central. Case series of children with steroid-Induced glaucoma
Allergic conjunctivitis, particularly a severe form called vernal keratoconjunctivitis, is common in pediatric populations and often treated with steroid drops. Because children may not complain of visual changes until the damage is advanced, and because parents and general practitioners may not realize that an over-the-counter or prescribed steroid drop carries this risk, children on prolonged steroid treatment need the same pressure monitoring that adults get, if not more.
Managing a Steroid Response
The first and simplest step when a steroid response is detected is to stop or reduce the offending drug. In many cases, IOP returns to normal within days to weeks after the steroid is withdrawn. The challenge arises when the steroid is medically necessary, as it often is after eye surgery or for inflammatory conditions that threaten vision.
One practical strategy is switching to a steroid that is less likely to raise pressure. Newer agents like loteprednol etabonate and rimexolone were specifically designed to provide anti-inflammatory benefit with less impact on IOP.14PubMed Central. Intraocular pressure effects of common topical steroids for post-cataract inflammation: are they all the same? Loteprednol in particular has shown a favorable safety profile. In a study of known steroid responders, patients on loteprednol had a modest, non-statistically-significant IOP increase (from about 17 to 22 mmHg over six weeks), while those on prednisolone acetate saw their pressures jump from about 18 to 27 mmHg.15PubMed. Intraocular pressure response to loteprednol etabonate in known steroid responders The chemical structure of loteprednol also makes it less likely to contribute to cataract formation, another common steroid side effect.16PubMed Central. Advances in corticosteroid therapy for ocular inflammation: loteprednol etabonate
When switching steroids is not enough, or when the steroid cannot be stopped, doctors turn to pressure-lowering eye drops, the same medications used for ordinary glaucoma. For the majority of patients who develop elevated IOP after intravitreal steroid injections, drops alone are sufficient to control the pressure.17PubMed Central. Elevated Intraocular Pressure After Intravitreal Steroid Injection in Diabetic Macular Edema: Monitoring and Management
When Drops Are Not Enough
A small percentage of steroid responders develop pressures that resist medical therapy, or they need to remain on high-dose steroids long term for serious systemic or ocular conditions. For these patients, procedural options exist.
Selective laser trabeculoplasty (SLT), a quick office-based laser treatment applied to the drainage tissue, has been shown to be safe and effective for steroid-induced pressure elevation. One study found an average IOP reduction of roughly 9 mmHg after SLT, with nearly all patients able to discontinue their pressure-lowering drops afterward.18PubMed. Selective Laser Trabeculoplasty for Steroid-Induced Ocular Hypertension following Endothelial Keratoplasty A broader review similarly concluded that SLT provides well-controlled IOP in this population.19PubMed. Outcomes of selective laser trabeculoplasty in corticosteroid-induced ocular hypertension and glaucoma
For advanced or refractory cases, minimally invasive glaucoma surgeries (MIGS) or traditional filtering surgeries may be needed. One study looked at a technique called trabectome surgery in steroid-induced glaucoma patients and found an average pressure reduction from about 34 mmHg before surgery to 15 mmHg at one year, a roughly 56% drop, while also reducing the number of daily glaucoma medications from nearly four to about two.20PubMed Central. Outcome of primary trabeculotomy ab interno (Trabectome) surgery in patients with steroid-induced glaucoma Notably, half the patients in that study were still on their steroid treatment after surgery and the other half had tapered or stopped. The surgery managed the pressure even in many patients who continued the drug causing the problem.
A Systemic Trait, Not Just an Eye Trait
One of the more intriguing findings in this area is that steroid responsiveness does not seem to be limited to the eye. Older research found that when steroid responders were given a small oral dose of dexamethasone, their blood cortisol levels dropped more than in non-responders. The correlation was striking: the bigger the eye-pressure response someone had previously shown, the more their cortisol was suppressed by the oral dose.21JAMA Ophthalmology. Depression of Plasma Cortisol and the Steroid Ocular Pressure Response
This finding hints that steroid responsiveness reflects something about how an individual’s cells react to glucocorticoids throughout the body, not just in the trabecular meshwork. Supporting this idea, a study of 100 patients found a strong correlation between how sensitive a patient’s blood lymphocytes (a type of white blood cell) were to corticosteroids in a lab dish and how much their eye pressure rose during steroid treatment.22PubMed. In vitro corticosteroid: correlation response with primary open-angle glaucoma and ocular corticosteroid sensitivity In other words, the eye’s response seems to be one visible manifestation of a whole-body trait. Whether this systemic corticosteroid sensitivity has consequences beyond eye pressure, such as different responses to steroid therapy for asthma, arthritis, or autoimmune disease, remains an open and largely unstudied question. The research linking eye responsiveness to systemic cellular sensitivity was mostly done decades ago and has not been followed up with modern molecular tools, leaving a gap that pharmacogenomics researchers are only now beginning to revisit.