Screening family members most effective for detection, study shows

BOSTON – The most efficient way to detect primary open-angle glaucoma cases may be by screening first-degree relatives with the disease, according to a study reported here at the World Glaucoma Congress.

“Due to its low prevalence in the general population, screening for [primary open-angle glaucoma] may have a low predictive value of a positive test,” S. Fabian Lerner, MD, and colleagues said in a poster presentation. “Screening of high-risk groups may yield better results. If having a first-degree relative with glaucoma is a risk factor for developing the disease, a detection campaign focused in the relatives of glaucoma patients would have more probabilities of detection.”

The study screened 61 relatives of 35 glaucoma patients for primary open-angle glaucoma and 50 control subjects older than 55 years. A complete ophthalmic examination was performed on each subject.

Dr. Lerner and colleagues found that 26.2% of family members of glaucoma patients were diagnosed with the disease. In comparison, 6% of control group subjects were diagnosed with the disease, a statistically significant difference.

Increased iris thickness, curvature, area linked to angle closure

Increased iris thickness, curvature and area are risk factors for angle closure, even after adjusting for other known ocular risk factors, according to a study.

In the community-based, cross-sectional, observational study, 2,047 patients older than 50 years of age without ophthalmic symptoms were recruited from a community clinic in Singapore. All patients underwent gonioscopy and anterior segment optical coherence tomography. Angle closure was defined as the presence of at least 180· of angle in which the posterior pigmented trabecular meshwork was not visible on gonioscopy in primary position.

Norlina Ramli, MD, said of the 1,465 eyes available for analysis, 315 patients (21.5%) had angle closure. Mean curvature and iris thickness were greater in the patients with angle closure.

“Anatomical variations in iris parameters — curvature, thickness and area — independent of anterior chamber depth and axial length are associated with narrow angles. These associations are particularly stronger in women and older people 60 years of age and older,” Dr. Ramli said.

POAG patients show perfusion pressure variations

Primary open-angle glaucoma (POAG) patients show a distinct behavior of perfusion pressure, according to a presentation.

“The 24-hour evaluation of IOP and perfusion pressure shows a striking difference between the glaucoma patients and healthy controls, especially at night. The current management of glaucoma may be incomplete because it is not possible to measure IOP and perfusion pressure at night,” Vital P. Costa, MD, said.

Dr. Costa compared the IOP, blood pressure and perfusion pressure variations of 29 primary open-angle glaucoma patients and 24 healthy subjects throughout a 24-hour time period. IOP and blood pressure measurements were taken every 2 hours from 8 a.m. to 6 a.m., with the IOP measurements taken in the supine position from midnight to 6 a.m.

Mean IOP measurements in the glaucoma patients were significantly higher than the healthy subjects at all times. Mean systolic blood pressure was significantly higher in glaucoma patients from 4 a.m. to 10 a.m. and also from 2 p.m. to 6 p.m. Mean diastolic blood pressure was higher in patients from 8 a.m. to 10 a.m. but was lower at 4 a.m.

Dr. Costa said the glaucoma patients had higher systolic perfusion pressures during the morning from 8 a.m. to 10 a.m. but lower diastolic perfusion pressures during the night from midnight to 6 a.m.

Patients with thicker RNFL show more diffuse loss

No constant retinal nerve fiber layer (RNFL) decline was found in patients with preperimetric glaucoma, according to a poster presentation.

Csilla Ajtony, MD, and colleagues at the University of Pécs in Pécs, Hungary, evaluated the rate and pattern of visual field changes in preperimetric glaucoma. The study examined 112 eyes of 112 patients with optic nerve head changes typical for glaucoma but no visual function changes.

In the study, 23 eyes (20%) had visual field progression during 3.7 years of follow-up, of which 16 (69%) were patients with average RNFL less than 80 µm at baseline. Patients with thicker RNFLs lost 2.44 µm per year and had a more diffuse pattern of retinal nerve fiber loss.

The authors said the results — even with individual variability — support mean RNFL thickness around 70 µm, representing “a profound threshold value in glaucomatous structural changes. Implications of these findings may have importance when evaluating progress on the disease.”

Consider biological measurements, family history factors

Glaucoma diagnosis and therapy should be based on biological measurements such as corneal thickness and cup-to-disc ratio and risk factors such as family history, not race, a physician said.

Eve J. Higginbotham, MD, spoke about how race in glaucoma is largely a social issue, not a biological one. She said clinicians should consider a patient’s country of origin and family history to be the most specific and significant risk factors for the disease.

“If we keep thinking about people in just these four or five [racial] categories, I think we’re missing the opportunity to identify more specific biological causes related to apparent responses to therapy,” Dr. Higginbotham said.

Anthropological research and genetic research have shown that race does not have a role in the scientific community, but it continues to play a role in the medical community, she said.

“When you think about the social implications, particularly in this country, such as access to care and the effectiveness of the relationship between physicians and patients, one might consider using race along those lines,” Dr. Higginbotham said.

According to Robert D. Fechtner, MD, of the Institute of Ophthalmology and Visual Science, UMDNJ-New Jersey Medical School, “Our teaching and traditions in medicine sometimes are not helpful as we expand our understanding of a disease such as glaucoma. Dr. Higginbotham makes this clear in her discussion of using biological measurements as the basis for diagnosis and treatment of glaucoma.”

Dr. Fechtner said in an interview that clinicians can do better than try to determine risk or treatment plan based on race. “As we gain greater insights into the genetic and molecular foundations for glaucoma and variation in response to treatment we will find little use for some of our older concepts,” he said. “It is useful to understand the limitations of these historical concepts.”

Link between POAG, mortality unclear

The relationship between POAG and patient mortality remains unknown, according to a physician.

Louis R. Pasquale, MD, presented results of his meta-analysis of nine population-based studies.

“Primary open-angle glaucoma is a poorly understood form of neurodegeneration. Blood pressure, diabetes and body mass index are associated with increased mortality, which are positively related to IOP. But the relationship to primary open-angle glaucoma is complex and controversial. The answer to the question ‘Can primary open-angle glaucoma kill you?’ is not intuitively obvious,” Dr. Pasquale said.

He said his study of the nearly 3,000 cases of primary open-angle glaucoma did not support an association between POAG and all-cause or cardiovascular mortality.

However, the study was unable to control for treatment, and he was unable to perform meta-regression by race. Variation in disease definition and disease misclassification also could have had unpredictable effects on the study’s outcome. The majority of the studies did not control for blood pressure, diabetes or body mass index.

“The true relationship between primary open-angle glaucoma and mortality remains unknown,” Dr. Pasquale said. “Future analyses should use incident cases and control for treatment and covariance.”

Communication key to addressing noncompliance

The main reason cited by glaucoma patients for noncompliance is “forgetting to use drops,” but the true reason could be dislike for taking the medications, a fact that physicians should be aware of when addressing compliance, a glaucoma expert said.

“Is forgetting a barrier? I don’t think so. I think forgetting is an excuse. It’s a socially acceptable lie. ‘I didn’t not take them because I didn’t want to take them, I forgot.’ And so I think that’s what patients are telling us a lot of time when they say, ‘I forget to take my drops,’” David S. Friedman, MD, MPH, said at a symposium supported by an educational grant from Pfizer.

Dr. Friedman said communication between the physician and patient is key to addressing patient noncompliance. He and colleagues conducted a study examining reasons for noncompliance and found that 40% of patients cited forgetfulness for nonadherence.

About 16% of patients were concerned about side effects, 16% ran out of drops, 11% stopped taking drops during travel, 9% did not take drops away from home, 8% did not use drops correctly, and 8% were concerned about their eyes’ appearance, according to the study.

Consider evidence-based guidelines

The principles of glaucoma treatment options and the importance of evaluating each patient individually were among the topics presented at the “New Guidelines for Glaucoma” symposium sponsored by the European Glaucoma Society.

John Thygesen, MD, said the goal of evidence-based glaucoma therapy is to lower IOP, and treatment decisions should be made for each patient on an individual basis.

Anton Hommer, MD, spoke about how combined medications fit in the glaucoma management algorithm. He said the decision to switch medications or add additional medications is an important issue, and clinicians must consider any side effects, effectiveness and the patient’s tolerability.

The ideal combination therapy will significantly lower IOP, Dr. Hommer said.

In his review of incisional surgery options for glaucoma patients, Tarek Shaarawy, MD, said surgery depends on the surgeon’s preferences, as well as the pathology, economics, visual potential and patient’s desire.

“We really have to look at the risk-benefit of all glaucoma surgery. We owe it to our patients to make the right decision,” Dr. Shaarawy said.

He added that among future challenges for surgeons is to find new surgical technologies to not only decrease IOP, but also increase safety and the patient’s quality of life after the procedure.

Early detection, assessment of risk factors improve treatment

If glaucoma is diagnosed and treated early, patients benefit in numerous ways, including prevention of vision loss and enhancement of treatment regimens and physician-patient relationships.

“Earlier diagnosis and earlier treatment is likely to put the patient in a very much better position in terms of obtaining useful vision for the remainder of their lives,” Ivan Goldberg, MBBS, FRANZCO, FRACS, said. “There’s more time to fine-tune our dynamic treatment strategies. There’s more time for us to build that essential therapeutic alliance with the patient.”

At the Hot Topics in Glaucoma Care symposium, partly sponsored by an educational grant from Alcon, Dr. Goldberg said clinicians should analyze their approach to assessing risk factors for early diagnosis. In developing a patient’s therapeutic index, physicians may begin with a static profile, establishing baseline assessment of damage and risk.

In treating glaucoma patients, physicians often use a dynamic profile, assessing ongoing damage and risk levels. He outlined the South East Asia Glaucoma Interest Group’s “decision square” for assessing glaucomatous damage.

“This balance between assessment of risk and disease status is something we can do automatically,” Dr. Goldberg said.

Douglas J. Rhee, MD, commented that advanced damage at the time of initial diagnosis is one of the most consistent prognostic factors for the risk of going blind from glaucoma. “Thus, earlier detection of disease or disease progression through a more precise risk assessment of various patient factors offers several possible benefits, as outlined by Dr. Goldberg,” he said. “The South East Asia Glaucoma Interest Group’s ‘decision square’ provides guidance on how acute the need may be to rapidly control IOP based on the disease status (stable, uncertain or progressing) and the risk factor profile (increased, uncertain, stable). These practical algorithms can provide a quick tool to help guide the clinician’s thought process for the management of an individual patient.”