Associate Professor Mark Roth
BSc(Pharm) BAppSc(Optom) PGCertOcTher NECO FAAO
Ocular surface disease in patients using antiglaucoma eye-drops
According to a study published in Optometry and Vision Science, patients using topical antiglaucoma eye-drops have a significantly higher occurrence of ocular surface disease than those who are not on any medications.
Ramli and colleagues conducted a cross-sectional, case-comparison study to assess the prevalence of ocular surface disease (OSD) in relation to various medications.
The researchers compared OSD presence among 105 glaucomatous participants using topical antiglaucoma medications and 102 control participants not using topical medications. OSD presence was evaluated using Ocular Surface Disease Index (OSDI) questionnaire grading, corneal staining, Schirmer’s test and the tear film break-up time (TBUT) test.
It was found that more glaucoma participants had corneal staining, moderate OSDI symptoms and abnormal Schirmer’s tests than control participants. An association was found between abnormal TBUT and higher numbers of topical medications and eye-drops that contained benzalkonium chloride (BAK).
Significantly, participants using an eye-drop with BAK were three times more likely to show abnormal OSDI. The authors suggested that the number of ocular surface disease cases may increase with the growing number of eye-drops that contain the preservative BAK.
Ramli N et al. Optom Vis Sci 2015; doi: 10.1097/OPX.0000000000000542.
Sleep quality in patients linked to glaucomatous structural damage
The authors of a cross-sectional study have found that decreased function of intrinsically photosensitive retinal ganglion cells (ipRGC) affects pupillary response and sleep quality.
Both eyes were tested on the patients in the study (45 participants – 32 with glaucoma and 13 healthy subjects). Pupillary light reflex and polysomnography were used to evaluate the function of ipRGCs and correlate it with structural damage in glaucoma.
For pupillary light reflex, glaucoma patients had significantly lower peak responses to the 250 cd/m2 blue flash and the average rapid eye movement latency and lower sustained responses to the 250 cd/m2 blue flash and arousal parameters, both associated with a thinner mean RNFL.
For the polysomnography, a thinner mean RNFL thickness was associated with a poorer oxygen desaturation index in glaucoma patients.
Patients with glaucoma had significantly lower average total sleep time, sleep efficiency and minimum oxyhaemoglobin saturation compared with the healthy subjects. Patients with glaucoma had significantly higher arousal durations after falling asleep and more periodic limb movements.
The authors suggested that concerns about sleep disturbances in patients with glaucoma should be incorporated into clinical evaluations.
Gracitelli C et al. Ophthalmology 2015; 122: 6: 1139-1148.
The shifting tide of opinion on antibiotics
Articles published in the Medical Journal of Australia are encouraging health-care providers to stop antibiotic treatment when the patient feels better, rather than finish their full course of antibiotics.
Professor Gwendolyn Gilbert, of the Marie Bashir Institute for Infectious Diseases and Biosecurity at the University of Sydney, wrote that there was no risk, but ‘every advantage’ in stopping a course of an antibiotics once a bacterial infection had been excluded and ‘minimal risk’ if signs and symptoms of a mild infection had resolved.
For most infections, Professor Gilbert wrote, ‘there was no solid evidence for the recommended duration of therapy, while for many syndromes associated with bacteraemia, studies showed no difference in outcome when shorter courses of antibiotics were used.’
Professor Chris Del Mar, professor of public health at the Centre for Research in Evidence-Based Practice at Bond University, Queensland, concurred, saying in an interview with MJA InSight ‘the old mantra about finishing a course of antibiotics was based on an assumption that unless you eradicated the infection it could come back and you would need another course of antibiotics—but there is no evidence for this except in a few very specific illnesses such as tuberculosis.’
Professor Del Mar said he hoped that Australia would move towards a system where health-care practitioners prescribed the exact amount of antibiotic required, specific to the individual patient and their illness.
Greater co-operation was needed between GPs at the local level to agree on which antibiotics would be prescribed for which illnesses, to reduce the risk of antibiotic resistance developing in certain locales, he said.
‘There is a common misconception that resistance will emerge if a prescribed antibiotic course is not completed,’ Professor Gilbert wrote. ‘However, premature cessation of antibiotic therapy will not increase the risk that resistance will emerge. For most infections, the recommended duration of therapy (5–14 days, depending on syndrome) is based on expert opinion and convention, rather than solid evidence.’
Gilbert G. Intrinsically photosensitive retinal ganglion cell activity is associated with decreased sleep quality in patients with glaucoma. Med J Aust 2015; 202: 3: 121-122.
Testing the Triggerfish
How good is a contact lens sensor (CLS) for 24-hour monitoring of IOP-related short-term patterns compared with IOP obtained by pneumatonometry? Pretty good.
In this prospective clinical trial, 31 healthy volunteers and two glaucoma patients were housed for 24 hours in a sleep laboratory. One randomly-selected eye was fitted with a CLS (Triggerfish, Sensimed, Switzerland), which measures changes in ocular circumference. In the contralateral eye, IOP measurements were taken using a pneumatonometer every two hours with subjects in the habitual body positions.
Performance of CLS was defined in two ways.
1. Recording the known pattern of IOP increase going from awake (sitting position) to sleep (recumbent), defined as the wake/sleep (W/S) slope.
2. Accuracy of the ocular pulse frequency (OPF) concurrent to that of the HR interval. Strength of association between overall CLS and pneumatonometer curves was assessed using coefficients of determination (R2).
The W/S slope was statistically significantly positive in both eyes of each subject (CLS, 57.0 ± 40.5 mVeq/h, p < 0.001 and 1.6 ± 0.9 mmHg/h, p < 0.05 in the contralateral eye). In all, 87 CLS plots concurrent to the HR interval were evaluated. Graders agreed on evaluability for OPF in 83.9 per cent of CLS plots. Accuracy of the CLS to detect the OPF was 86.5 per cent.
The researchers concluded that CLS measurements compare well to the pneumatonometer and may be of practical use for detection of sleep-induced IOP changes. The CLS also is able to detect ocular pulsations with good accuracy in a majority of eyes.
Mansouri K, Weinreb RN, Liu JH. Efficacy of a contact lens sensor for monitoring 24-h intraocular pressure related patterns. PLoS One 2015; 10: 5: e0125530. doi: 10.1371/journal.pone.0125530.
Metformin for pre-diabetic patients
Metformin, which was first synthesised in 1922 and shown to lower blood glucose, has become one of the most prescribed drugs in the world. Fresh debate on the use of the drug has flared following a study that suggested that the drug was still under-prescribed.
In the retrospective cohort study ‘Metformin Prescription for Insured Adults with Prediabetes From 2010 to 2012’,1 researchers concluded that metformin was rarely prescribed for diabetes prevention in working age adults.
In the study, researchers examined health insurance claims data to assess metformin use among a national sample group of more than 17,000 adults (age range, 19-58) with pre-diabetes between 2010 and 2012. Researchers found that only 3.7 per cent of patients received metformin. They concluded that the barriers to wider adoption of metformin as a safe, tolerable, evidence-based and cost-effective pre-diabetes therapy should be scrutinised.
Reviewing the study in the NEJM, Dr Jamaluddin Moloo was openly sceptical of the finding. ‘We don’t know whether giving metformin to [pre-diabetic patients] will eventually pay off in clinically meaningful reductions in mircrovascular or macrovascular complications,’ he wrote.
Dr Moloo cited a recent reanalysis of Diabetes Prevention Program data,2 which suggested that metformin delayed progression to formal diagnoses of diabetes in a relatively small subgroup of prediabetic patients who were at highest baseline risk for progression.
In that study, researchers found that the benefit of metformin was seen almost entirely in patients in the top quarter of risk of diabetes. No benefit was seen in the lowest risk quarter.
1. Moin T et al. Metformin prescription for insured adults with prediabetes from 2010 to 2012: a retrospective cohort study. Ann Intern Med 2015; 162: 8: 542-548.
2. Sussman et al. Improving diabetes prevention with benefit based tailored treatment: risk based reanalysis of Diabetes Prevention Program. BMJ 2015; Feb 19; 350: h454. doi: 10.1136/bmj.h454.
Metformin for open angle glaucoma
According to a study online by JAMA Ophthalmology, Metformin may decrease the risk of open angle glaucoma (OAG) in people with diabetes.
To determine if medications that mimic caloric restriction—such as metformin—can reduce the risk of age-associated eye diseases, researchers from the University of Michigan examined metformin use and the risk of open-angle glaucoma (OAG) using data from a large US managed care network from 2001 through 2010.
Study results indicate that patients prescribed the highest amount of metformin (greater than 1,110 grams in two years) had a 25 per cent reduced risk of OAG risk compared with those who took no metformin. Every one gram increase in metformin was associated with a 0.16 per cent reduction in OAG risk, which means that taking a standard dose of two grams of metformin per day for two years would result in a 20.8 per cent reduction in risk of OAG.
Other diabetes medications did not confer a similar OAG risk reduction. The study authors concluded that these results illustrate the importance of understanding the potential impact of caloric restriction mimetic drugs such as metformin on the risk of developing medical conditions that affect older persons.
Lin H-Chang et al. Association of geroprotective effects of metformin and risk of open-angle glaucoma in persons with diabetes mellitus. JAMA Ophthalmol. Published online May 28 2015. doi:10.1001/jamaophthalmol.2015.1440
Intraretinal oedema the source of visual aberrations
A study has found that increased higher order (HO) wavefront aberrations are present in eyes with macular oedema.
In the prospective study, 33 eyes of patients with diabetic macular oedema were scanned with a ray-tracing wavefront device. As a control group, wavefront aberrometry was performed in 31 patients. Ocular and internal aberrations and visual quality metrics were evaluated separately to determine whether the source of aberrations was ocular or internal.
There was a statistically significant difference between the groups in internal higher order (HO) root mean square (0.34 +/- 0.24 vs 0.16 +/- 0.05), HO Strehl ratio (0.08 +/- 0.05 vs 0.18 +/- 0.09), and modulation transfer function (0.29 +/- 0.1 vs 0.4 +/- 0.1). There was no statistically significant difference in Strehl ratio and HO root mean square between phakic and pseudophakic patients. Height of cystoid spaces was a significant predictor (p < 0.001) of Strehl ratio.
The study authors concluded that in eyes with macular oedema, internal HO wavefront aberrations were greater than in control eyes. The authors suggested that the increase in HO wavefront error seemed visually relevant, and pointed to increased intraretinal oedema as the source of higher order aberrations.
Miháltz K et al. Ocular wavefront aberrations and optical quality in diabetic macular edema. Retina 2015; Jun 3. [Epub ahead of print].
First-in-class cholesterol-lowering drug recommended to FDA
An advisory committee has recommended that the Food and Drug Administration (FDA) approve two PCSK9 inhibitors for the reduction of low-density lipoprotein (LDL) in certain patient populations.
The panel voted to recommend approval of the monoclonal antibody alirocumab (Praluent), and evolocumab (Repatha) during the Endocrinologic and Metabolic Drugs Advisory Committee meeting on June 10, 2015.
Panel members recommended that both drugs initially be limited to patients with familial hypercholesterolaemia until more data are available on whether the drugs actually reduce cardiovascular events.
Studies have found that alirocumab reduces LDL cholesterol by 40 per cent to 60 per cent, compared with placebo, while evolocumab was associated with a roughly 60 per cent LDL reduction.
The FDA is not required to follow the recommendations of its advisory panels, but it usually does. If approved, the injectable drugs would be the first available proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, which help the liver remove LDL cholesterol from the blood.
Endocrinologic and Metabolic Drugs Advisory Committee, FDA Briefing Document [monograph on the Internet]. 2015 (cited 2015 July 24).
IOP-lowering effect of SLT and ALT comparable
There is no difference between the IOP-lowering effect of selective laser trabeculoplasty (SLT) and argon laser trabeculoplasty (ALT), according to results of a systematic review published in Eye.
The investigator reviewed randomised controlled trials (RCTs) published in peer-reviewed journals comparing SLT to other glaucoma treatment options. The main outcome measure was the change in IOP from baseline.
According to the study, an initial search of PubMed identified 23 RCTs, with 17 meeting the inclusion criteria. Nine RCTs compared 180-degree SLT to 180-degree ALT, and one trial compared 360-degree SLT to 360-degree ALT; all reported no difference in terms of IOP reduction from baseline.
The author concluded that in terms of the IOP lowering effect, there is no difference between SLT and ALT. Three trials indicate no difference between 360-degree SLT and medical therapy, with one of the trials indicating greater IOP reduction with latanoprost over 90 degrees and 180 degrees SLT. Three trials indicate no difference between 180-degree SLT and 360-degree SLT. It is inconclusive whether 90 degrees is less efficacious than 180 degrees SLT. One trial reports greater IOP reduction with ELT over 180 degrees SLT in the long term.
McAlinden C. Eye (Lond). [published online ahead of print]. doi:10.1038/eye.2013.267.
Lucentis listed for DME and RVO
In July, Minister for Health Sussan Ley issued a statement that announced that the Australian government would expand the listing of the Pharmaceutical Benefits Scheme to include Lucentis to treat diabetic macular oedema and retinal vein occlusion.
‘Patients with a range of serious eye conditions now have affordable access to life-changing medicines that normally cost up to $10,000 for treatment,’ Ley said. ‘Eighteen thousand Australian patients will now pay $6.10 (concessional) or $37.70 (general) for Lucentis.’
‘Diabetic macular oedema is a complication of diabetes, and retinal vein occlusion is a blockage of the vessel which drains blood out of the retina, the light-sensitive tissue at the back of the eye, and if left untreated both conditions can lead to severe vision loss and blindness. Lucentis is effective in slowing or stopping the progression of these degenerative conditions,’ Ley said. ‘Without treatment for these conditions patients can suffer severe loss of vision and blindness and therefore lose their independence.’
This new listing will assist about 12,000 patients per year with diabetic macular oedema and 6,000 patients per year with retinal vein occlusion.