Laird Harrison

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A fixed-dose tafluprost and timolol combination eye drop led to significant reductions in intraocular pressure (IOP) in patients with open-angle glaucoma (OAG) and ocular hypertension (OHT) in a safety and efficacy study, demonstrating its benefit in patients intolerant to, or insufficiently controlled on, prostaglandin analogue (PGA) monotherapy or topical beta-receptor blockers.

“The severity of most clinical signs and subjective symptoms decreased significantly compared to that on the previous treatment, and in general the [drug] was well tolerated,” reported Francesco Oddone and colleagues at Istituto di Ricovero e Cura a Carattere Scientifico (IRCSS) Fondazione Bietti, Rome, Italy. They published the findings of Santen’s Visionary study in Advances in Therapy.

When attempting to reduce IOP in glaucoma patients, clinicians typically begin treatment with PGA monotherapy and then move to combination therapy if monotherapy does not achieve the target IOP reduction. However, preservatives such as benzalkonium chloride (BAK) used in many topical glaucoma therapies have been shown to worsen ocular surface disease (OSD), with preservative-induced OSD manifesting in 45-60% of chronically treated glaucomatous eyes.

Because of the dangers of patients developing this disease, researchers have been experimenting with preservative-free topical treatments for glaucoma, such as the fixed combination of tafluprost (0.0015%) and timolol (0.5%). The eye drops are marketed under the trade name Taptiqom in Europe (Loyada in Italy).

The randomised, controlled, real-world Phase IV trial, Visionary, enrolled 713 patients (577 of whom completed the study) and monitored patient outcomes over a 6-month period. Patients were all adults suffering from OAG or OHT who had medically recorded insufficient IOP reduction with, or poor tolerance for, beta-receptor blocker or PGA monotherapy.

Study participants also had to have been evaluated by an investigator ophthalmologist and determined to be likely to benefit from a preservative-free drops formulation. Researchers did not include patients in the study if they had had ophthalmologic surgery in the previous 6 months; had previously been treated with PF tafluprost/timolol FC treatment; were pregnant or breastfeeding at the screening visit; or had any contraindication against tafluprost or timolol treatment.

Patients were instructed to treat their glaucomatous eyes with one drop of the preservative-free combination daily and their IOP was measured using Goldmann applanation tonometry at week 4, week 12 and month 6. In addition to IOP data, researchers asked patients to evaluate subjective symptoms such as dry eye feeling, irritation, itching, foreign body sensation and eye pain at each visit using a four-grade scale (none, mild, moderate and severe). They evaluated ocular signs at month 6 and compared them with the baseline measures in all participants.

The absolute mean IOP change at month 6 was statistically significant (p < 0.0001). Mean (SD) IOP reduction from baseline was 5.7 (4.11) mmHg, which represents an overall IOP reduction of 24.9%. 40% of study participants reported IOP reduction of 30% or greater.

Of the 577 participants included in the analysis, 81.3% had changed to preservative-free tafluprost/timolol treatment due to uncontrolled IOP, while 18.4% were enrolled due to low ocular tolerance on the previous topical IOP-lowering medication (regardless of the success of the IOP control).

At month 6, the average IOP reduction from baseline was 26.6% for participants who had experienced poor IOP control when using previous treatments, while those patients who had switched to preservative-free tafluprost/timolol treatment due to low tolerance of previous treatments enjoyed a mean IOP reduction of 19.6% (p < 0.001).

Researchers observed a mean corneal fluorescein staining (CFS) score reduction from baseline at month 6 in 32.7% of patients, while 53.6% showed no change, and CFS increased in 13.6% of the patients.

A proportion of patients (17%) stopped using PF tafluprost/timolol FC treatment during the study period. Of these 98 patients, two had poor IOP reduction; 12 had poor local tolerance; four dropped out due to poor compliance; and 13 stopped for “other reasons.” Data is unavailable for the 67 other patients.

Ninety-nine (17.2%) of the 577 patients involved in the safety analysis reported 129 adverse effects during the 6-month study period, although only 69 (53.5%) were considered to be treatment-related. Only one of the adverse events was considered serious (status asthmaticus) while 93% were mild to moderate in severity. Of the adverse events, 71.3% had resolved or were resolving at the point of data cut-off.

The researchers said they were encouraged by the results of their study, but cautioned that more research is needed in paediatric populations, as well as those of non-European origin and those patients suffering from angle-closure glaucoma.

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Preservative-free tafluprost/timolol lowers IOP well, glaucoma study shows

The COVID-19 virus can cause ocular complications such as conjunctivitis, though not necessarily in the early stages of the disease, according to researchers.

Samples taken from the eyes of a patient suffering from conjunctivitis 13 days into his illness tested positive for SARS-CoV-2, the coronavirus that causes COVID-19, wrote Lu Chen of the Shenzhen Eye Hospital in Shenzhen, China. Dr Chen and colleagues published their findings in the British Journal of Ophthalmology.

The observation suggests that the virus could spread from the conjunctiva, the researchers said, adding that on the other hand, the conjunctiva may not be the ideal site for sampling for early diagnostic tests for the virus.

The patient, a 30-year-old man, presented to a local hospital with diarrhoea and a sore throat on 4 February, 2020. He reported that he had been in contact with someone diagnosed with COVID-19 from 28 to 30 January, and first experienced his own symptoms on 3 January.

Using a reverse transcription polymerase chain reaction (RT-PCR) assay, the hospital detected SARS-CoV-2 RNA in the patient’s nasopharyngeal swabs. As a result, doctors there referred him to an isolation ward designated for confirmed COVID-19 cases at the Third People’s Hospital of Shenzhen.

Doctors here tested for other viral respiratory pathogens but did not find any. They found his vital signs within normal ranges, except his body temperature, which was 37.3°C. Lung auscultation showed rhonchi.

They administered umifenovir, lopinavir and ritonavir, and supplied supportive care. Gradually, the patients’ sore throat and diarrhoea subsided, but on the 13th day of his illness he reported redness, foreign body sensation and tearing in both eyes.

In the right eye, best-corrected visual acuity was logMAR 0.10; in the left eye it was 0.05. Bilateral moderate conjunctival infection, watery discharge, inferior palpebral conjunctival follicles and tender palpable preauricular lymph nodes appeared on slit lamp examination, but without subconjunctival haemorrhage, pseudomembrane, corneal lesions or anterior chamber inflammation.

Fundus examination and macular ultrastructure measurements with optical coherence tomography did not reveal anything remarkable. Routine bacterial and fungal cultures were negative.

The doctors swabbed the lower fornix of each eye without topical anaesthesia, and identified SARS-CoV-2 RNA with RT-PCT on the 14th day of the patient’s illness. The cycle threshold of 31 indicated a moderate quantity of virus in the conjunctival swabs, but much less than the 23.52 cycle threshold in the nasopharyngeal specimens and 25 in the sputum specimens. (Cycle threshold is inversely proportional to viral load.) The physicians prescribed ribavirin eye drops four times per day and continued slit lamp examinations.On the 15th day of the patient’s illness, the patient’s ocular symptoms began to resolve and by day 19, he said they were gone. A slit lamp examination confirmed a reduction of both the bilateral conjunctival injection and the follicles on the inferior palpebral conjunctiva.

“This case report highlights the necessity to further understand the full spectrum, duration and natural history of ocular complications associated with SARS-CoV-2 infection to inform clinical treatment and affect precaution practices,” the researchers wrote.

Other coronaviruses have been associated with conjunctivitis in humans and in animals with retinal disorders. And a retrospective test of conjunctival samples showed SARS-CoV-2 RNA in one of 30 samples. But the researchers could not find any previous reports of SARS-CoV-2 associated with conjunctivitis in a human patient.

“The fact that our patient developed acute viral conjunctivitis with positive SARS-CoV-2 tests in conjunctival swab samples indicated that SARS-CoV-2 could indeed cause ocular complications but not necessarily in the early stage of illness,” the researchers concluded.

COVID-19 implicated in conjunctivitis

Rohingya refugees are three- to six-times more likely to be blind than the native Bangladeshi population, but there are replicable, low-cost models for provide effective eye care in crisis settings, a new study by the NGO Orbis International suggests.

Researchers reporting in PLOS Medicine compared vision screening results obtained from February 2018 to March 2019 between displaced Rohingya refugees based in the Kutupalong refugee settlement in Cox’s Bazar, Bangladesh, and local residents, as part of a cohort study.

They found that adult Rohingya had significantly worse eyesight than the equivalent age group of the 'host population' (p < 0.001), with the prevalence of blindness measured as visual acuity <3/60. However, Rohingya children aged 5-17 had better visual acuity than the host cohort.

Vision loss in both populations was primarily due to uncorrected refractive error and unoperated cataracts, with cataracts a particularly significant problem for working-age Rohingya adults. Compared to their counterparts in the host population, this group suffered substantially more from cataracts if they were aged 18-29 (4.67% versus 1.8%; p = 0.0019), 30-39 (7.61% versus 2.39%; p < 0.001) or 40-49 (7.91% versus 3.77%; p = 0.0014).

Between February 2018 and March 2019, Orbis screened a total of 48,105 Rohingya refugees in the Kutupalong settlement and 20,357 local host community residents from four surrounding subdistricts. Rohingya refugees received screenings in two fixed Camps (denoted 4 and 11) of the settlement.

Of those included in the study, 71.6% were children and 46.5% were female. Members of the host population sample were screened in vision care centres at local hospitals and schools. Of the these participants, 88.5% were children and 54.4% were female.

Patient screenings included examination of the anterior segment by hand light; vision assessment separately in each eye using a Snellen E chart; refraction by a trained a refractionist for any eye with presenting vision <6/12: and (in cases of suspected cataracts) dilation of the pupil.

Orbis provided spectacles free-of-charge to study participants who suffered from refractive error and researchers diagnosed the presence of cataracts using standard practices.

An ophthalmologist used a slit lamp to examine the anterior segment and performed direct ophthalmoscopy with dilation of the pupil to confirm a suspected diagnosis of cataract on screening, before measuring intraocular pressure, axial length and corneal curvature, blood sugar and blood pressure.

Patients with best-corrected visual acuity of 6/36 due to cataracts were referred for surgery, and the corrective procedure was made available to study participants with a visual acuity of up to 6/18 upon request. The operations were generally performed in one eye only.

Children who had failed the eye examination were treated at a specially constructed child-friendly department at the local secondary facility, the Cox’s Bazar Baitush Sharaf Hospital.

The study had a number of limitations. The researchers were careful to note that because the study was focused on clinic-based assessments, it was unable to provide the same results as a population-based survey.

In addition, the voluntary nature of the study meant that neither the Rohingya refugee sample nor the host sample were likely to be representative of the overall populations from which they were drawn. Dr Ahmed (the study author) and his team are hopeful, however, that their work can provide a model for more research into, and treatment of, visual impairment among refugee populations.

In recent decades, refugee populations have reached an all-time high, with the United Nations High Commissioner for Refugees estimating a total of 70.8 million displaced persons in camps around the world. Although there has been a growth in awareness of the necessity for treating chronic and acute medical conditions in people in conflict or crisis situations, research into refugees’ ophthalmological needs has lagged behind, and there are few documented models to deliver vision services in such settings, according to the researchers.

Visually impaired people are at an increased risk of poverty, with evidence demonstrating improvements in quality-of-life and increased household income following cataract surgery, according to the study. More research is needed to explore the impact of vision care on the well-being of displaced populations, the team concluded.

Visual impairment high among Rohingya refugees

Clinicians may soon be able to use genetic information alone to determine the risk of myopia in very young children, researchers believe.

“A personalised medicine approach to detecting children at risk of myopia is now feasible, although currently the accuracy of [polygenic risk scores] is not yet good enough to warrant their use in clinical practice,” wrote Neema Ghorbani Mojarrad and colleagues at the University of Bradford in Bradford, UK. They published their findings in JAMA Ophthalmology.

At present, the best predictor of the risk of myopia in children is a low hyperopic refractive error at an age before myopia typically manifests, so clinicians seeking to evaluate the risk in young children typically rely on a screening regimen of cycloplegic autorefraction. Successfully predicting the likelihood of children developing myopia can help clinicians recommend lifestyle changes such as spending more time outdoors, which can help mitigate or prevent the development of the refractive error.

However, the use of cycloplegic autorefraction is time and resource-intensive, so Mr Mojarrad and his team wanted to see if they could develop a polygenic risk score (PRS) for evaluating risk based purely on genetic information. To develop their PRS, the researchers conducted three genome-wide association studies (GWASs). Data used for the GWASs included 287,448 UK Biobank participants who had not undergone autorefraction, and 95,619 who had undergone noncycloplegic autorefraction.

In addition, researchers collected data on 328,917 individuals whose information had originally been compiled to study the relationship between genes and years of educational attainment, and had been downloaded from the Social Science Genetic Association Consortium (SSGAC) website. They then combined their data in a meta-analysis in order to increase the effective sample size, before generating a PRS for each participant using genotypes for 1.1 million variants.

The investigators validated their PRS by using it to predict rates of myopia in 1,516 women whose genome data and known rates of myopia were obtained from the Avon Longitudinal Study of Parents and Children (ALSPAC).
	The PRS derived from the SSGAC GWAS provided limited predictive accuracy (R2 = 0.14%, where R2 = 100% would be a completely accurate prediction). The autorefraction and non-autorefraction GWASs were also relatively inaccurate (R2 = 7.1% versus R2 = 6.9%).

The researchers were able to improve the accuracy of the PRS by combining sets of traits. The best result came from combining the autorefraction and non-autorefraction GWASs (R2 = 10.8%). Combining all three traits yielded even greater accuracy (R2 = 11.2%).

The GWAS was unable to produce a PRS that was as reliable as the results obtainable using cycloplegic autorefraction. Measured in terms of the under the receiver operating characteristic (AUROC), where 0.5 is a useless model and 1 is a perfect model, the PRS had an AUROC of 0.67 while the cycloplegic autorefraction scored 0.87.

While they were unable to develop a suitably accurate alternative to cycloplegic autorefraction for predicting rates of myopia, Mr Mojarrad and his team were able to conclude from their study that children can be categorised into three groups based on their risk of developing myopia. Those with a PRS in the top 25% were 3-5 fold more likely to develop the condition, those in the top 10% had a 3.5-6 fold increased risk, whilst the likelyhood was 4.5-6.5 fold higher for those in the top 5%.

The researchers are hopeful that this information will aid clinicians in recommending lifestyle interventions or prescribing orthokeratologic or atropine treatment. They predict that future research may lead to the development of a PRS that will enable doctors to accurately predict myopia in children, obviating the need for cycloplegic autorefraction.

Author | Laird Harrison

Articles

COVID-19 implicated in conjunctivitis

Visual impairment high among Rohingya refugees

Genetics analysis may predict myopia in children

Preservative-free tafluprost/timolol lowers IOP well, glaucoma study shows