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Dr Laura Downie
BOptom PhD(Melb) PGCertOcTher FACO FAAO DipMus(Prac) AMusA


Prognostic value of mfERG and OCT in eyes undergoing pan-retinal photocoagulation for diabetic retinopathy

A clinical study conducted in China has investigated the prognostic utility, on visual acuity (VA), of multifocal electroretinography (mfERG) and optical coherence tomography (OCT) in eyes undergoing pan-retinal photocoagulation treatment for diabetic retinopathy.

Patients with severe non-proliferative diabetic retinopathy or early proliferative diabetic retinopathy were included. MfERG and OCT data were captured prior to pan-retinal photocoagulation; final VA was recorded six months after treatment.

Among the 42 eyes included, 31 eyes (73.8 per cent) had improved or stable VA; 11 eyes (26.2 per cent) showed deterioration in VA six months after pan-retinal photocoagulation. VA was significantly correlated with the amplitude and latency of the multifocal electroretinography. On OCT, the integrity of both the foveal ellipsoid zone of the photoreceptors and external limiting membrane, as well as macular thickness, correlated with final VA.

It was concluded that lower amplitude of multifocal electroretinography and disrupted foveal ellipsoid zone status on OCT were most significantly correlated with a worse visual prognosis in diabetic eyes undergoing pan-retinal photocoagulation.

Invest Ophthalmol Vis Sci; 2014. Aug 21, Epub ahead of print.


Early diabetic macular oedema screening critical

A cross-sectional analysis of 1,038 patients with diabetes sought to estimate the prevalence of diabetic macular oedema in the US population, and to identify associated risk factors. Patients were derived from the 2005 to 2008 National Health and Nutrition Examination Survey.

From examination of retinal fundus photographs, 55 persons were identified as having diabetic macular oedema (overall weighted prevalence: 3.8 per cent; 95 per cent CI: 2.7-4.9 per cent); no differences in prevalence were evident by age or sex. Elevated glycosylated haemoglobin A1c (hbA1c, OR 1.47; 95 per cent CI: 1.27-1.71 for each 1 per cent; p < 0.001) and longer duration of diabetes (OR 8.51, 95 per cent CI: 3.70-19.54 for = 10 versus < 10 years; p < 0.001) were associated with a higher prevalence of diabetic macular oedema.

The results suggest a greater burden of diabetic macular oedema among individuals with high hbA1c levels and/or longer disease duration. Given recent treatment advances in reducing vision loss and preserving vision in persons with diabetic macular oedema, it is imperative that all persons with diabetes receive early screening. This recommendation is even more important for those at higher risk of macular oedema.

JAMA Ophthalmol 2014; Aug 14. Epub ahead of print.


Monthly versus as-needed ranibizumab injections in patients with retinal vein occlusion

This randomised, open-label, vision-examiner masked, 15-month study compared pro re nata (prn) and monthly intra-vitreal injections of 0.5 mg ranibizumab in retinal vein occlusion (RVO) patients, who had been previously stabilised by monthly injections.

Subjects (n = 193) had macular oedema secondary to branch or central RVO and initially received monthly injections of 0.5mg ranibizumab for seven months. Subjects meeting stability criteria between seven and 14 months were randomised (1:1) to prn injections versus continued monthly injections. Non-randomised subjects (n = 13), who did not meet the stability criteria, continued to receive monthly injections.

The primary outcome measure was the slope of change of best-corrected visual acuity (BCVA) between months seven and 15.

There was no significant difference in the slope of change in BCVA between months seven and 15 in patients treated prn (n = 80) versus those treated with monthly injections (n = 80; p = 0.509). The percentage of subjects who achieved a BCVA of 6/12 or better at month 15 was 76.8 per cent in the prn group, 71.3 per cent in the monthly group, and 46.2 per cent in the non-randomised subjects.

It was concluded that following oedema-resolution from seven or more monthly ranibizumab injections in RVO subjects, visual outcomes at month 15 were overall excellent and did not significantly differ in subjects treated as-needed compared with those who maintained monthly injections.

Ophthalmology 2014; July 21. Epub ahead of print.


Aniseikonia linked to central retinal thickness

Aniseikonia after pneumatic retinopexy for rhegmatogenous retinal detachment may be related to the pre-operative macular status.

A prospective, interventional case series study investigated 30 patients who had undergone pneumatic retinopexy, as the initial procedure for management of a rhegmatogenous retinal detachment. Primary outcomes included: visual acuity, post-operative aniseikonia, anatomical success and measurement of central retinal thickness using OCT. Each outcome was measured post-operatively at three, six and 12 months.

Of the 30 eyes, there were 17 cases of macula-off retinal detachment and 13 cases of macula-on retinal detachment. All eyes had an anatomically successful surgical repair, as evident with OCT. Three months after pneumatic retinopexy, 18 patients (60 per cent) developed micropsic aniseikonia; aniseikonia was diagnosed in 15 patients (88.2 per cent) in the macula-off retinal detachment group, with two patients (11.8 per cent) unaffected.

In the macula-on retinal detachment group, three patients (23.1 per cent) had aniseikonia, while 10 patients (76.9 per cent) were unaffected. The presence of aniseikonia was strongly linked to the difference in central retinal thickness, between the operated eye and the fellow eye, 12 months post-operatively.

Macula-off retinal detachment patients had a higher incidence of aniseikonia, compared to macula-on retinal detachment patients, following retinal re-attachment. There was a moderate to high correlation between the grading of aniseikonia and the inter-eye difference in central retinal thickness.

Am J Ophthalmol 2014; Aug 12. Epub ahead of print.


OCT for patients with juvenile multiple sclerosis

Between three and 10 per cent of patients with juvenile multiple sclerosis (MS) experience early-onset disease before the age of 18 years.

An observational, cross-sectional study was conducted at two academic MS centres in Germany. The aim was to assess whether OCT measurements of retinal nerve fibre layer thickness (RNFLT) and total macular volume (TMV) could be useful for differentiating retinal axonal and neuronal damage in patients with a history of early-onset MS.

RNFLT and TMV were compared in three groups of subjects: early-onset MS patients (n = 36; mean age of onset: 15.5 ± 2.0 years), age- or disease-duration matched later-onset MS patients (n = 58), and healthy controls (n = 32).

Compared with controls, early-onset MS subjects showed significant reductions in RNFLT and TMV, independent of a history of optic neuritis. RNFLT loss in early-onset MS patients was similar to that observed in later-onset MS patients; TMV loss was slightly higher compared with disease-duration-matched later-onset MS subjects.

In a generalised estimating model, the early-onset MS group displayed a similar correlation between disease duration and RNFLT or TMV loss to later-onset MS patients.

These data suggest that there are significant degrees of retinal axonal and neuronal damage in early-onset MS patients. These findings may provide a structural basis for the observation that early-onset MS patients reach states of irreversible disability at a younger age than later-onset MS patients.

Eur J Neurol 2014; Aug 7. Epub ahead of print.


Impaired blood flow regulation linked to glaucoma

The arteriovenous difference in oxygen saturation in primary open angle glaucoma (POAG) eyes may reflect decreased retinal oxygen demand due to glaucomatous loss of neuroretinal rim tissue.

POAG subjects (n = 41; aged: 64.1 ± 12.9 years) and age-matched controls (n = 40) underwent imaging (centred at the optic disc margin) using the Retinal Vessel Analyser (RVA). Retinal vessel diameters were calculated as central retinal artery-equivalent (CRAE) and vein-equivalent (CRVE), from diameter measurements in peri-papillary vessels. Oxygen saturation of the arterioles and venules were investigated. After taking baseline measurements, the vascular response to flicker light exposure was investigated.

At baseline, the mean oxygen saturation of the retinal venules was higher in POAG eyes than in controls (4.36 ± 7.11 versus 59.78 ± 8.47, p = 0.01), whereas the mean arterio-venous oxygen saturation difference was lower (33.07 ± 5.24 versus 37.53 ± 6.95, p = 0.002). Arterial oxygen saturation, as well as arterial and venous diameters, showed no significant difference between groups.

Increases in the CRVE during flicker light stimulation (3.72 ± 3.29 per cent versus 5.43 ± 4.04, p = 0.04), as well as the change of venous oxygen saturation (2.08 ± 3.74 per cent versus 4.18 ± 3.88 per cent, p = 0.016) and the arteriovenous saturation difference (-2.1 ± 3.31 per cent versus -4.43 ± 3.6 per cent, p = 0.003) were smaller in POAG eyes than in control eyes.

It was concluded that the lower extent of flicker-induced change to retinal venules was suggested to potentially indicate an impairment of blood flow regulation.

Graefes Arch Clin Exp Ophthalmol 2014; Aug 12. Epub ahead of print.


Mutations contribute to the pathogenesis of keratoconus

Mutations in the zinc finger protein gene, ZNF469, cause recessive Brittle Cornea syndrome, characterised by spontaneous corneal perforations. Genome-wide association studies (GWAS) have implicated common variants in this gene as a determinant for central corneal thickness (CCT).

A study investigated the contribution of ZNF469 in a sample of keratoconus patients (n = 43; 49 per cent being Maori or Pacific, Polynesian). Mutational analysis of ZNF469 was undertaken using Sanger sequencing, including an ancestrally-matched Polynesian control population. Bio-informatic databases of exome variation, and protein prediction software were used to determine presence and frequency, and pathogenicity for each observed change.

Fourteen non-synonymous missense single-nucleotide polymorphisms were observed in ZNF469. Of the 43 probands, at least one probable disease-causing variant was detected in 20 (46 per cent) (16/32 sporadic, 4/11 familial) and two variants in 5, (11.6 per cent) (3/32 sporadic, 2/11 familial). Only heterozygous changes segregated with disease. Three ‘deleterious’ changes observed in the Polynesian controls were removed from analysis, therefore pathogenic variants occurred in 10/43 (23.3 per cent).

Rare, missense mutations in ZNF469, predicted to be pathogenic, occurred heterozygously, at a frequency of 23 per cent in a keratoconus population. ZNF469 is associated with central corneal thickness in genome-wide association studies, and therefore likely to play a role in the synthesis and/or organisation of corneal collagen fibres. It was concluded that the pathogenic changes observed either genetically predispose towards a ‘thin’ cornea, which then becomes keratoconic, or are directly pathogenic.

Invest Ophthalmol Vis Sci 2014; Aug 5. Epub ahead of print.

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