Glaucoma; confocal scanning laser ophthalmoscopy; screening; stereo photographs; intraobserver variability
birdshot retinochoroidopathy; optical coherence tomography
Medical Education; Imaging
Epidemiology; Eye Lids; Conjunctiva
Paraneoplastic melanocytic proliferation (bilateral diffuse uveal melanocytic proliferation, BDUMP) is a rare but devastating disease that causes progressive visual loss in patients who usually have an occult malignancy. Visual loss occurs as a result of paraneoplastic changes in the uveal tissue.
In a masked fashion, the serum of two patients with BDUMP was evaluated for the presence of cultured melanocyte elongation and proliferation (CMEP) factor using cultured human melanocytes. We evaluated the efficacy of plasmapheresis as a treatment modality early in the disease in conjunction with radiation and chemotherapy.
The serum of the first case patient was investigated after plasmapheresis and did not demonstrate proliferation of cultured human melanocytes. The serum of the second case was evaluated prior to treatment with plasmapheresis and did induce this proliferation. These findings are in accordance with the diminution of CMEP factor after plasmapheresis. Treatment with plasmapheresis managed to stabilise the ocular disease progression in both patients.
In the past, visual loss due to paraneoplastic melanocytic proliferation was considered progressive and irreversible. We treated two patients successfully with plasmapheresis and demonstrated a relation between CMEP factor in the serum of these patients and proliferation of cultured melanocytes.
Retina; Imaging; Choroid; Neoplasia
To analyse ab interno trabeculectomy (AIT) with the trabectome and combined phacoemulsification with AIT (phaco-AIT) by Shaffer angle grade (SG).
Prospective study of AIT and phaco-AIT with narrow angles of SG≤2 versus open angles ≥3. Outcomes included intraocular pressure (IOP), medications, complications, secondary surgery and success (IOP <21 mm Hg and >20% reduction without further surgery). Exclusion criteria were missing preoperative data and <1 year follow-up.
Of 671 included cases, at 1 year AIT SG≤2 (n=43) had an IOP reduction of 42% from 27.3±7.4 to 15.7±3.0 mm Hg (p<0.01) versus AIT SG≥3 (n=271) with an IOP reduction of 37% from 26.1±7.8 to 16.4±3.9 mm Hg (p<0.01). In phaco-AIT with SG≤2 (n=48), IOP was reduced 24% from 20.7±7.0 to 15.7±3.6 mm Hg (p<0.01) versus phaco-AIT with SG≥3 (n=309) with an IOP reduction of 25% from 22.6±6.4 to 17.0±3.4 mm Hg (p<0.01). There was no difference between SG≤2 and SG≥3 in reduction of IOP or medications, complications, secondary surgery and success rates (p>0.05).
SG≤2 is not associated with worse outcomes in AIT or phaco-AIT.
Glaucoma; Treatment Surgery; Anterior chamber; Angle
Ciliary neurotrophic factor (CNTF) has been shown to protect retinal ganglion cells (RGCs) in traumatic optic nerve injury. We sought to evaluate this neuroprotective effect of CNTF after an ischaemic event using rodent anterior ischaemic optic neuropathy (rAION), a mouse model of non-arteritic anterior ischaemic optic neuropathy (NAION).
We induced rAION in Thy1-cyan fluorescent protein (CFP) transgenic mice by exposing the optic nerve to frequency doubled neodymium yttrium aluminium garnet laser pulses following intravenous rose bengal injection. One day after rAION induction, an intravitreal injection of 0.75 μg CNTF or vehicle (sham injection) was given. Animals were euthanised on day 15 after induction, tissues isolated and CFP cells in the RGC layer were counted using stereology in flat-mounted retina. The average number of CFP-positive (CFP+) cells was determined for each study group and the percentages of RGC loss were compared between the different groups.
Two weeks after rAION induction, significantly more (CFP+) cells were preserved in CNTF-treated eyes than in sham-injected controls. Sham-treated animals showed a 58% loss of CFP+ cells. In contrast, CFP+ cell density in CNTF-treated eyes decreased by only 10%, when compared with untreated control eyes. This increased survival was statistically significant (p<0.05).
CNTF exerts a neuroprotective effect in ischaemic optic nerve injury and promotes RGC survival, suggesting that CNTF may be effective in the clinical treatment of human NAION.
To determine the diagnostic accuracy of telemedicine in various clinical levels of diabetic retinopathy (DR) and diabetic macular oedema (DME).
PubMed, EMBASE and Cochrane databases were searched for telemedicine and DR. The methodological quality of included studies was evaluated using the Quality Assessment for Diagnostic Accuracy Studies (QUADAS-2). Measures of sensitivity, specificity and other variables were pooled using a random effects model. Summary receiver operating characteristic curves were used to estimate overall test performance. Meta-regression and subgroup analyses were used to identify sources of heterogeneity. Publication bias was evaluated using Stata V.12.0.
Twenty articles involving 1960 participants were included. Pooled sensitivity of telemedicine exceeded 80% in detecting the absence of DR, low- or high-risk proliferative diabetic retinopathy (PDR), it exceeded 70% in detecting mild or moderate non-proliferative diabetic retinopathy (NPDR), DME and clinically significant macular oedema (CSME) and was 53% (95% CI 45% to 62%) in detecting severe NPDR. Pooled specificity of telemedicine exceeded 90%, except in the detection of mild NPDR which reached 89% (95% CI 88% to 91%). Diagnostic accuracy was higher with digital images obtained through mydriasis than through non-mydriasis, and was highest when a wide angle (100–200°) was used compared with a narrower angle (45–60°, 30° or 35°) in detecting the absence of DR and the presence of mild NPDR. No potential publication bias was detected.
The diagnostic accuracy of telemedicine using digital imaging in DR is overall high. It can be used widely for DR screening. Telemedicine based on the digital imaging technique that combines mydriasis with a wide angle field (100–200°) is the best choice in detecting the absence of DR and the presence of mild NPDR.
Diagnostic tests/Investigation; Telemedicine; Retina
To assess the efficacy and safety of latanoprostene bunod (LBN) compared with latanoprost 0.005%, and to determine the optimum drug concentration(s) of LBN in reducing intraocular pressure (IOP) in subjects with open angle glaucoma or ocular hypertension.
Randomised, investigator-masked, parallel-group, dose-ranging study. Subjects instilled one drop of study medication in the study eye once daily each evening for 28 days and completed five study visits. The primary efficacy endpoint was the reduction in mean diurnal IOP at Day 28.
Of the 413 subjects randomised (LBN 0.006%, n=82; LBN 0.012%, n=85; LBN 0.024%, n=83; LBN 0.040%, n=81; latanoprost, n=82), 396 subjects completed the study. Efficacy for LBN was dose-dependent reaching a plateau at 0.024%–0.040%. LBN 0.024% led to significantly greater reductions in diurnal IOP compared with latanoprost at the primary endpoint, Day 28 (p=0.005), as well as Days 7 (p=0.033) and 14 (p=0.015). The incidence of adverse events, mostly mild and transient, was numerically higher in the LBN treatment groups compared with the latanoprost group. Hyperaemia was similar across treatments.
LBN 0.024% dosed once daily was the lower of the two most effective concentrations evaluated, with significantly greater IOP lowering and comparable side effects relative to latanoprost 0.005%. LBN dosed once daily for 28 days was well tolerated.
Clinical trial number
Clinical Trial; Drugs; Glaucoma; Intraocular pressure; Treatment Medical
There is an increasing recognition that visuocognitive difficulties occur in children with neurodevelopmental problems. We obtained normative data for the performance of primary school children using three tests of visuocognitive function that are practicable in a clinical setting.
We tested 214 children aged between 4 and 11 years without known developmental problems, using tests to assess (1) orientation recognition and adaptive movement (postbox task), (2) object recognition (rectangles task) and (3) spatial integration (contours task).
96% could do the postbox task with ease—only 4% (all aged <9 years) exhibited minor difficulties. Errors in the rectangles task decreased with age: 33% of children aged 4–5 years had major difficulties but >99% of children aged ≥6 years had no, or minor, difficulties. Median scores for the contours task improved with age, and after age 8 years, 99% could see the contour using long-range spatial integration rather than density.
These different aspects of children’s visuocognitive performance were testable in a field setting. The data provide a benchmark by which to judge performance of children with neurodevelopmental problems and may be useful in assessment with a view to providing effective supportive strategies for children whose visuocognitive skills are lower than the expectation for their age.
Visual perception; Child health (paediatrics); Epidemiology; Rehabilitation; Diagnostic tests/Investigation
To describe the imaging standards, grading protocol and baseline characteristics of polypoidal choroidal vasculopathy (PCV) from the EVEREST study.
In a prospective, multicentre study, confocal scanning laser ophthalmoscope indocyanine green angiography (ICGA) was performed using a standardised imaging protocol. All images were graded using standardised, calibrated equipment by fellowship-trained ophthalmologists at the Central Reading Center.
Sixty-one patients with PCV were included in the study. ICGA characteristics included: nodular appearance stereoscopically (56 eyes, 91.8%), hypofluorescent halo (42, 68.9%), abnormal vascular network (54, 88.5%) and pulsation of the polyps (4, 6.6%). Colour fundus photography revealed orange subretinal nodules (34, 55.7%) and massive submacular haemorrhage (8, 13.1%). The mean area of the PCV lesion was 3.11 mm2 (range, 0.2–10.7 mm2). The vascular channels filled within 7.3–32.0 s (mean: 17.9 s) while the mean filling time for polyps was 21.9 s (range, 7.3–40.4 s). Patients with massive submacular haemorrhage were less likely to have abnormal vascular channels seen on ICGA (28.6% vs 83.3% for those without massive haemorrhage, p=0.001).
The imaging and grading protocols and baseline characteristics of a multicentre, randomised controlled trial of PCV are described in detail, and may serve as reference for future randomised, controlled trials on PCV.
Clinical trial number
This work was supported by Novartis Pharma AG, Basel, Switzerland grant number NCT00674323 (clinicaltrials.gov).
Neovascularisation; Retina; Choroid; Macula
Epidemiology; Medical Education; Public health
Retinal cell remodelling has been reported as a consistent feature of ageing. However, the degree to which this results in transretinal degeneration is unclear. To address this, the authors used multiphoton microscopy to quantify retinal degeneration in postmortem human eyes of two age groups.
Retinas from six young subjects (18–33 years old) and six older subjects (74–90 years old) were prepared as wholemount preparations. All retinas were stained with 4,6-diamidino-2-phenylindole and imaged by multiphoton confocal microscopy to quantify neuron densities in the retinal ganglion cell layer (RGCL), inner nuclear layer (INL) and outer nuclear layer (ONL). Neurons were counted using automated cell identification algorithms. All retinas were imaged hydrated to minimise tissue artefacts.
In both groups, 56% of the area within the central 4 mm eccentricity and 27% of the area with eccentricity between 4 mm and 7 mm were imaged. Compared with young subjects, the peak RGCL neuron loss in the aged subjects (25.5%) was at 1 mm eccentricity. INL and ONL neuron densities significantly decreased at 1–2 mm eccentricity (8.7%) and 0.5–4 mm eccentricity (15.6%) respectively (P <0.05). The reduction in neuron density in the INL corresponded, spatially, to the region with the greatest neuron loss in the RGCL and ONL.
This is the first study to correlate neurodegeneration in different populations of cells in the ageing retinas. These data confirm that the greatest neuronal loss occurs in the RGCL and ONL in human ageing retinas, whereas the INL is relatively preserved.