New technology predicts conversion to POAG

Clinicians can predict which patients with ocular hypertension (OHT) are most likely to develop primary open-angle glaucoma (POAG) using short-wave automated perimetry (SWAP), scanning laser polimetry (SLP) and confocal laser ophthalmoscopy (CSLO), as well as the patient’s age, according to researchers.

"Our study suggests that the combination of patient age with structural and functional variables provided by various instruments could help the clinician in better managing a general population of OHT patients, even if a predictive model alone cannot replace clinical judgment," writes Maria L Salvetat and colleagues.

Dr Salvetat and her colleagues from Azienda Ospedaliero-Universitaria Santa Maria della Misericordia in Udine, Italy, published their findings in Eye.

Although lowering intraocular pressure (IOP) often benefits patients with POAG, it’s not feasible to lower the IOP in everyone with ocular hypertension because of its prevalence, and because of the risk of adverse effects. As such, it would be useful to know which patients with ocular hypertension are at greatest risk of developing POAG.

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Previous large studies have identified older age, higher IOP, larger vertical or horizontal cup-to-disk ratio, greater standard automated perimetry (SAP), pattern standard deviation (PSD) and thinner central corneal thickness (CCT) as significant predictors.

Race, positive family history and low diastolic perfusion pressure have also been documented as risk factors.

But new instrumental tests have shown the ability to detect fundamental or morphological glaucomatous damage. Besides SWAP, SLP and CSLO, these include frequency-doubling technology (FDT) and Heidelberg retina tomography (HRT).

A test with ibopamine has also showed promise. A D₁-dopamine and alpha-adrenergic agonist, ibopamine induces an increased aqueous humour production and a noncycloplegic mydriasis when instilled in the conjunctival sac.

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In previous studies, ibopamine eye drops caused an IOP increase in patients with reduced functioning of the outflow structures, including patients with POAG, normal tension glaucoma, positive family history, and hydrodynamic disorders caused by corticosteroids. Healthy patients, on the other hand, tend to show no influence on IOP with ibopamine.

To see which of these methods was most helpful in predicting the conversion to POAG, the researchers randomly selected one eye in each of 133 patients with ocular hypertension.

All the patients had IOPs at least 24 mm Hg in one eye and greater than 21 mm Hg in the other eye. They all had normal optic disc and retinal nerve fibre layer (RNFL) appearance in both eyes, 2 normal standard automated perimetry visual field (SAP VF) test results in both eyes, best corrected visual acuity at least 0.7, open anterior chamber angles, absence of other ocular pathology, reliable SAP, SWAP and FDT test results, and good CSLO and SLP image quality.

Assessing the results

While all patients were untreated at baseline, some received IOP therapy during the study.

After 10 years, 29 of the 116 (25%) patients who completed the study developed POAG.  The mean conversion time was 48 months, with a range of 12–84 months.

In a multivariate analysis, the researchers found a statistically significant difference between converters and non-converters for the following parameters: older age (hazard ratio [HR] 1.0); SWAP Glaucoma Hemifield test outside normal limts (HR 4.3); greater SLP inter-eye symmetry (HR 1.1); lower CSLO rim volume (HR 1.1); and greater CSLO cup-to-disc ratio.

Gender, IOP, CCT, ibopamine test results, SAP and FDT variables were comparable between groups, so the researchers did not deem them predictive for glaucoma conversion.

These results differed with earlier studies finding that higher IOP, thinner CCT and greater SAP pattern standard deviation (PSD) at baseline were predictive.

The researchers speculated that the discrepancy could be ascribed to such factors as the number and race of the people in the study populations, anti-glaucoma therapy, data collection methods used, visual field and optic disc evaluation methods, and definitions of ocular hypertension and conversion to glaucoma.

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They suggested a different reason for the failure of FDT to predict glaucoma in this study. The test gave rise to a high percentage of abnormal results in their cohort. While the percentage of patients with abnormal FDT results was similar to that reported by other authors, this number was greater than the number that would be expected to convert to glaucoma, which raised the possibility that the high sensitivity of FDT in detecting early glaucomatous damage could be partly explained by false positive results.

Salvetat and her colleagues could not find any other studies that examined the predictive ability of the ibopamine test for conversion to POAG. They found the results of this test to be very poor, with a sensitivity of 69% and a specificity of 41.4%, suggesting that a large proportion of the patients had a reduced outflow of the aqueous humour, even if many did not go on to develop POAG.

In this study, 86.2% of converters received treatment during the study period compared with 77% of non-converters, perhaps because the clinicians identified them as most likely to develop the disease.

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The results were in agreement with several previous studies, which showed that structural damage can often be detected several years before the development of visual field defects.

The researchers acknowledged several limitations to their study.  They didn’t assess all the factors that previous studies have identified as predictive of POAG, including family history, myopia, diabetes, race, cardiovascular disease, systemic blood hypotension and hypertension, ocular perfusion pressure, and local and systemic therapy.

Study limitations

The authors only examined baseline variables, although intercurrent risk factors might aid in prediction.

They did not have access to the exact recruitment process data, so they didn’t know how many patients were approached, how many were considered ineligible, and how many did not give consent to the study.

They included both treated and untreated eyes, and treatment with various anti-glaucoma medications. The optic disc assessment was also subjective, even though highly trained graders performed the assessments in a standardised manner.

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Finally, their findings might not be broadly applicable because some risk factors in their cohort might have a more important role than in other populations.

They concluded by calling for prospective studies based on larger populations, with longer follow-ups and additional parameters.