Patients with autoimmune polyendocrinopathy-candiasis-ectodermal dystrophy (APECED) develop severe keratoconjunctivitis, corneal scarring and visual loss, but the precise pathogenesis is unknown. This study evaluated the ocular surface immune cell environment, conjunctival goblet cell density and response to desiccating environmental stress of the autoimmune regulatory (Aire) gene knockout murine model of APECED.
Aire-deficient and wild type (WT) mice were subjected to desiccating stress from a drafty, low-humidity environment and pharmacological inhibition of tear secretion for 5 days. Immune cell populations (CD4+, CD8+, CD11b+, CD45+) and goblet cell density were measured in ocular surface tissues and meibomian glands, and compared with baseline values.
Greater CD4+ T cell populations were observed in the conjunctival epithelium of Aire-deficient mice (p<0.001) compared with WT. Aire-deficient mice also had greater numbers of CD4+, CD8+, and CD11b+ cells in the peripheral cornea at baseline and following desiccating stress. The meibomian glands of Aire-deficient mice demonstrated greater CD4+, CD8+, CD45+ and CD11b+ cells at baseline (p<0.001) and following desiccating stress. Conjunctival goblet cell density was lower at baseline and following desiccating stress in Aire-deficient compared with WT mice (p<0.001).
Aire-deficiency leads to infiltration of CD4+ and CD8+ T cells on the ocular surface and meibomian glands, which is accompanied by goblet cell loss. Desiccating stress promotes this proinflammatory milieu. Immune-mediated mechanisms play a role in the severe blepharitis and keratoconjunctivitis in the murine model of APECED.
To evaluate the effect of topical autologous plasma on nerve morphology in patients with neurotrophic keratopathy (NK) using the confocal microscope.
Eleven eyes of six patients with neurotrophic keratopathy were evaluated for this study. Corneal fluorescein staining was done, and corneal sensitivity measurements were done with the Cochet–Bonnet and modified Belmonte gas aesthesiometers. The Heidelberg Retina Tomograph 2 Rostock Cornea Module laser scanning confocal microscope was used to image the corneal surface and subepithelial neural plexus. Four images at the level of the subepithelial nerve plexus in the central cornea were randomly selected for analysis of the corneal nerves. Topical autologous plasma was used six to eight times per day.
The best-corrected visual acuity improved significantly after plasma treatment in all patients (p=0.003). The mean corneal fluorescein staining score significantly decreased after treatment (p=0.0003). There was a significant increase in corneal sensitivity measured by Cochet–Bonnet (p<0.0001) and modified Belmonte (p=0.01) aesthesiometers. The mean number, length, width and density of subepithelial nerves increased significantly after plasma treatment (p=0.0002).
In vivo confocal microscopy examination revealed preliminary evidence for improvement of corneal nerve findings suggesting efficacy of autologous plasma treatment in neurotrophic keratopathy.
Excessive lipid accumulation in Bruch’s membrane (BrM) is a hallmark of ageing, the major risk factor for age-related macular degeneration (AMD). Retinal pigment epithelial (RPE) cells may utilise reverse cholesterol transport (RCT) activity to move lipid into BrM, mediated through ATP-binding cassette A1 (ABCA1) and scavenger receptor BI (SR-BI).
ABCA1 expression was assessed by reverse transcription polymerase chain reaction (RT-PCR) and western blotting of human RPE cell extracts. Lipid transport assays were performed using radiolabelled photoreceptor outer segments (POS). ABCA1 and SR-BI expression was examined in normal mouse eyes by immunofluorescence staining. BrMs of ABCA1 and SR-BI heterozygous mice were examined microscopically.
Human RPE cells expressed ABCA1 mRNA and protein. The ABCA1 and SR-BI inhibitor glyburide (also known as glibenclamide) abolished basal transport of POS-derived lipids in RPE cells in the presence of high-density lipoprotein. Mouse retina and RPE expressed ABCA1 and SR-BI. SR-BI was highly expressed in RPE. BrMs were significantly thickened in SR-BI heterozygous mice, but not in ABCA1 heterozygous mice.
RPE cells express ABCA1 and SR-BI. This implies a significant role for SR-BI and ABCA1 in lipid transport and RCT in the retina and RPE.
The aim of this study was to describe an automated method for extracting quantitative measures of foveal morphology from optical coherence tomography (OCT) images of the human retina.
We performed a methodological study and retrospective investigation of selected cases. Sixty-five human subjects were included: 61 healthy subjects and four female carriers of blue-cone monochromacy (BCM). Thickness data from B-scans traversing the foveal pit were fitted to a mathematical model designed to capture the contour of the foveal surface. From this model, various metrics of foveal morphology were extracted (pit depth, diameter and slope).
Mathematical descriptions of foveal morphology enabled quantitative and objective evaluation of foveal dimensions from archived OCT data sets. We found a large variation in all aspects of the foveal pit (depth, diameter and slope). In myopes and BCM carriers, foveal pits were slightly less deep and had a more shallow slope, although these differences were not significant.
Offline analysis of OCT data sets enables quantitative assessment of foveal morphology. The algorithm works on the Stratus™ and Cirrus™ macular thickness protocols, as well as the Spectralis® and Bioptigen© radial-line scan protocols, and can be objectively applied to existing data sets. These metrics will be useful in following changes associated with diseases such as retinopathy of prematurity and high myopia, as well as in studying normal postnatal development of the human fovea.
To examine the practical improvement in image quality afforded by a broadband light source in a clinical setting and to define image quality metrics for future use in evaluating spectral domain optical coherence tomography (SD-OCT) images.
A commercially available SD-OCT system, configured with a standard source as well as an external broadband light source, was used to acquire 4 mm horizontal line scans of the right eye of 10 normal subjects. Scans were averaged to reduce speckling and multiple retinal layers were analysed in the resulting images.
For all layers there was a significant improvement in the mean local contrast (average improvement by a factor of 1.66) when using the broadband light source. Intersession variability was shown not to be a major contributing factor to the observed improvement in image quality obtained with the broadband light source. We report the first observation of sublamination within the inner plexiform layer visible with SD-OCT.
The practical improvement with the broadband light source was significant, although it remains to be seen what the utility will be for diagnostic pathology. The approach presented here serves as a model for a more quantitative analysis of SD-OCT images, allowing for more meaningful comparisons between subjects, clinics and SD-OCT systems.
To evaluate spectral-domain (SD) optical coherence tomography (OCT) reproducibility and assess the agreement between SD-OCT and Time-Domain (TD) OCT retinal nerve fibre layer (RNFL) measurements.
Three Cirrus-SD-OCT scans and one Stratus-TD-OCT scan were obtained from Diagnostic Innovations in Glaucoma Study (DIGS) healthy participants and glaucoma patients on the same day. Repeatability was evaluated using Sw (within-subject standard deviation), CV (coefficient of variation) and ICC (intraclass correlation coefficient). Agreement was assessed using correlation and Bland–Altman plots.
16 healthy participants (32 eyes) and 39 patients (78 eyes) were included. SD-OCT reproducibility was excellent in both groups. The CV and ICC for Average RNFL thickness were 1.5% and 0.96, respectively, in healthy eyes and 1.6% and 0.98, respectively, in patient eyes. Correlations between RNFL parameters were strong, particularly for average RNFL thickness (R2 = 0.92 in patient eyes). Bland–Altman plots showed good agreement between instruments, with better agreement for average RNFL thickness than for sectoral RNFL parameters (for example, at 90 μm average RNFL thickness, 95% limits of agreement were −13.1 to 0.9 for healthy eyes and −16.2 to −0.3 μm for patient eyes).
SD-OCT measurements were highly repeatable in healthy and patient eyes. Although the agreement between instruments was good, TD-OCT provided thicker RNFL measurements than SD-OCT. Measurements with these instruments should not be considered interchangeable.
Recent information suggests that the Age-Related Eye Disease Study (AREDS) supplement, enhanced intake of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), and reducing dietary glycaemic index (dGI) are protective against advanced age-related macular degeneration (AMD).
Dietary information was collected at baseline, and fundus photograph grades were obtained during the 8-year trial period from 2924 eligible AREDS AMD trial participants. Using the eye as the unit of analysis and multifailure Cox proportional-hazards regression, the risk of AMD progression was related to dietary intake in the four arms of the trial.
Independent of AREDS supplementation, higher intakes of DHA (≥64.0 vs <26.0 mg/day) (hazard ratio (HR) = 0.73, 95% confidence interval (CI), 0.57 to 0.94), EPA (≥42.3 vs <12.7 mg/day) (HR = 0.74, 95% CI 0.59 to 0.94), and lower dGI (dGI, <75.2 vs ≥81.5) (HR = 0.76, 95% CI 0.60 to 0.96) were associated with a lower risk for progression to advanced AMD. Participants consuming a lower dGI and higher DHA or EPA had the lowest risk (p value for synergistic interaction <0.001). Only participants in the “placebo” (p value for antagonistic interaction = 0.006) benefited from a higher DHA intake against early AMD progression (HR = 0.58, 95% CI 0.37 to 0.92; Ptrend = 0.01).
The findings show an association of consuming a diet rich in DHA with a lower progression of early AMD. In addition to the AREDS supplement, a lower dGI with higher intakes of DHA and EPA was associated with a reduced progression to advanced AMD.
Pain is a common feature of microvascular ischemic ocular motor cranial nerve palsies (MP). The natural history of pain in this condition has not been studied. The purpose of this report is to define the spectrum of pain in isolated MP, with special reference to diabetics versus nondiabetics.
Design and methods
Retrospective and prospective chart review was performed on 87 patients with acute onset MP of a single cranial nerve (CN III = oculomotor, CN IV = trochlear, or CN VI = abducens) that progressively improved or resolved over 6 months.
Five of the 87 patients had two events, making the total number events 92. There were 48 (52.2%) CN VI palsies, 39 (42.4%) CN III palsies, and 5 (5.4%) CN IV palsies. Thirty-six (41%) patients had diabetes. Pain was present in 57 (62%) events. The majority of diabetics and non-diabetics had pain. Pain preceded diplopia by 5.8 days (± 5.5) in one third of events. There was a trend towards greater pain with CN III palsies but this was not statistically significant. Patients who experienced severe pain tended to have pain for a longer duration of time (26.4 ± 21.7 days compared to 10.8 ± 8.3 and 9.5 ± 9 days for mild and moderate pain, respectively). There was no correlation between having diabetes and experiencing pain.
The majority of MP are painful, regardless of the presence or absence of diabetes. Pain may occur prior to or concurrent with the onset of diplopia. Nondiabetics and diabetics presented with similar pain characteristics, contrary to the belief that diabetics have more pain associated with MP.
Microvascular; cranial nerve; pain
To determine if retinal ganglion cell (RGC) loss influences the loss of surrounding RGCs to generate clustered patterns of cell death in human glaucoma. We hypothesise that retinal ganglion cell loss accelerates the loss of surrounding cells to generate, at a local, cellular scale, clustered patterns of retinal of RGC death. The absence of these interactions would result in a diffuse pattern of RGC loss.
Six glaucomatous retinas (67-83 years old) and six age-matched control retinas (61-89 years old) were prepared as wholemounts and stained by 4′,6-diamidino-2-phenylindole (DAPI) solution (3μg/mL in PBS). An area corresponds to central 14 degree of the visual field was imaged. The nearest neighbour distribution was determined for cells in both normal and glaucomatous RGCL.
We observed clustered RGC loss in human glaucoma on a background of diffuse loss. The mean nearest neighbour distance (NND) of the glaucomatous retinas was significantly higher compared with controls (p<0.001). The distribution of NND in glaucomatous retinas was skewed to the higher values with a higher positive kurtosis relative to controls. The quantitative analysis of the pattern of cell loss is supported by the visual inspection of the patterns of cell loss.
Nearest neighbour analysis is consistent with the presence of two patterns of cell loss in the RGCL in glaucoma. While the diffuse of cell loss can account for an overall reduction in the RGC population and additional non random pattern is consistent with the hypothesis that RGC loss has a local influence on the viability of surrounding cells.
To evaluate, within ocular imaging scans of acceptable quality as determined by manufacturers' guidelines, the effects of image quality on glaucoma discrimination capabilities.
One hundred and four healthy and 75 glaucomatous eyes from the Advanced Imaging in Glaucoma Study (AIGS) were imaged with GDx-VCC, HRT II and StratusOCT. Quality score (QS≥8), pixel standard deviation (SD≤50) and signal strength (SS≥5) were used as quality parameter cut-offs, respectively. GDx nerve fibre indicator (NFI) and HRT Moorfields regression analysis (MRA) classifications and OCT mean retinal nerve fibre layer (RNFL) thickness were used as the discriminatory parameters. Logistic regression models were used to model the dichotomous clinical classification (healthy vs glaucoma) as a function of image-quality parameters and discriminatory parameters.
Quality parameter covariates were statistically non-significant for GDx and HRT but had an inverse effect on OCT in predicting disease (a higher SS had a lower probability of glaucoma). Age was a significant covariate for GDx and HRT, but not OCT, while ethnicity and interaction between the image quality and the institute where scans were acquired were significant covariates in the OCT models.
Scan quality within the range recommended as acceptable by the manufacturer of each imaging device does not affect the glaucoma discriminating ability of GDx or HRT but does affect Stratus OCT glaucoma discrimination.
Retinoblastoma is the most common primary malignant intraocular neoplasm of childhood. The poor outcomes of patients with metastatic retinoblastoma have encouraged the search for new therapies. In the current study, the efficacy of combination therapy with calcitriol and cisplatin in athymic mice with subcutaneous Y-79 human retinoblastoma tumors was assessed.
60 athymic mice were subcutaneously injected with human Y79 retinoblastoma cells. Animals were randomized into four groups: group 1 - 50 μg of cisplatin; group 2 - 0.05 μg of calcitriol; group 3 - 0.05μg of calcitriol and 50 μg of cisplatin; group 4 - control. The cisplatin was administered once a week, and the calcitriol was given 5 times a week.
There was a significant inhibition of tumor growth in animals treated with the combination therapy of calcitriol and cisplatin as compared to controls and cisplatin alone (p=0.0001 and p=0.0041 respectively). In terms of toxicity, serum calcium levels were increased, but there was no mortality and minimal nephrotoxicity in any of the groups.
The present study shows that cisplatin given in combination with calcitriol may be a viable multidrug therapy option in the treatment of high risk retinoblastoma.
Calcitriol; Cisplatin; Retinoblastoma; Xenograft model
Maintenance of ocular viability is one of the major impediments to successful whole-eye transplantation. This review provides a comprehensive understanding of the current literature to help guide future studies in order to overcome this hurdle. A systematic multistage review of published literature was performed. Three specific questions were addressed: (1) Is recovery of visual function following eye transplantation greater in cold-blooded vertebrates when compared with mammals? (2) Is outer retina function following enucleation and reperfusion improved compared with enucleation alone? (3) Following optic-nerve transection, is there a correlation between retinal ganglion cell (RGC) survival and either time after transection or proximity of the transection to the globe? In a majority of the studies performed in the literature, recovery of visual function can occur after whole-eye transplantation in cold-blooded vertebrates. Following enucleation (and reperfusion), outer retinal function is maintained from 4 to 9 h. RGC survival following optic-nerve transection is inversely related to both the time since transection and the proximity of transection to the globe. Lastly, neurotrophins can increase RGC survival following optic-nerve transection. This review of the literature suggests that the use of a donor eye is feasible for whole-eye transplantation.
To study the long-term visual and anatomic outcomes of anti-vascular endothelial growth factor (VEGF) monotherapy for the treatment of patients with retinal angiomatous proliferation (RAP).
Retrospective review of patients who were diagnosed with AMD and RAP lesions, and who received anti-VEGF injections as the only mode of therapy.
20 eyes (15 patients; 9 women, 6 men) with RAP lesions treated by anti- VEGF were encountered. Mean patient age was 85.8 years (SD ± 4.54). Nine eyes were treated with intravitreal ranibizumab alone, 8 eyes with bevacizumab alone, and 3 eyes received both drugs. At the 1, 3 and 6 month follow-up the median VA had improved from baseline (20/72) to 20/52, (range: 20/25 to 20/400), 20/45 (range: 20/20 to 20/400), and 20/56 (range: 20/20 to 20/400), respectively, (P> 0.001, P= 0.001, and P= 0.05, respectively). At 24 month follow-up, the improvement of VA, defined as halving of the visual angle, occurred in 37.5% of the cases.
Anti-VEGF monotherapy represents a useful treatment option for RAP, with stable or improved visual acuity in 62.5% of patients at 2 years. 25% of eyes only required a single injection, however, in most cases (75%) repeated treatments were required, highlighting the need for long term follow up. Although in this small study, the results for visual improvement were not statistically significant beyond 3 months; our findings warrant further large-scale investigation.
age-related macular degeneration; bevacizumab; long term follow-up; ranibizumab; retinal angiomatous proliferation
To measure total retinal blood flow in normal human eyes using Doppler Fourier-domain optical coherence tomography (FD-OCT).
10 normal people aged 35 to 69 years were measured for the right eye using Doppler FD-OCT. Double circular scans around the optic nerve heads were used. Four pairs of circular scans that transected all retinal branch vessels were completed in 2 s. Total retinal blood flow was obtained by summing the flows in the branch veins. Measurements from the eight scans were averaged. Veins with diameters >33 μm were taken into account.
Total retinal blood flow could be measured in eight of 10 subjects: mean (SD) = 45.6 (3.8) μl/min (range 40.8 to 52.9 μl/min). The coefficient of variation for repeated measurements was 10.5%. Measured vein diameters ranged from 33.3 to 155.4 μm. The averaged flow speed was 19.3 (2.9) mm/s, which did not correlate with vessel diameter. There was no significant difference between flows in the superior and inferior retinal hemispheres.
Double circular scanning using Doppler FD-OCT is a rapid and reproducible method to measure total retinal blood flow. These flow values are within the range previously established by laser Doppler flowmetry.
To investigate retinal nerve fibre layer (RNFL) thickness measurement reproducibility using conventional time-domain optical coherence tomography (TD-OCT) and spectral-domain OCT (SD-OCT), and to evaluate two methods defining the optic nerve head (ONH) centring: Centred Each Time (CET) vs Centred Once (CO), in terms of RNFL thickness measurement variability on SD-OCT.
Twenty-seven eyes (14 healthy subjects) had three circumpapillary scans with TD-OCT and three raster scans (three-dimensional or 3D image data) around ONH with SD-OCT. SD-OCT images were analysed in two ways: (1) CET: ONH centre was defined on each image separately and (2) CO: ONH centre was defined on one image and exported to other images after scan registration. After defining the ONH centre, a 3.4 mm diameter virtual circular OCT was resampled on SD-OCT images to mimic the conventional circumpapillary RNFL thickness measurements taken with TD-OCT.
CET and CO showed statistically significantly better reproducibility than TD-OCT except for 11:00 with CET. CET and CO methods showed similar reproducibility.
SD-OCT 3D cube data generally showed better RNFL measurement reproducibility than TD-OCT. The choice of ONH centring methods did not affect RNFL measurement reproducibility.
To investigate whether the emulsification of conventional silicone oils can be reduced by adding small amounts of silicone molecules of a very long chain length.
Siluron 1000, Siluron 2000, Siluron 5000, Acri.Sil-Ol 5000, Oxane 5700, Densiron 68 LV, Densiron 68 and Densiron 68 HV (0.5 ml) were each tested along with either plasma or serum (0.5 ml) in a glass cuvette. Emulsification was induced by sonication and documented by photography. The total area of emulsified oil was assessed using the ImageJ software.
The addition of small amounts of very-long-chain silicone molecules significantly reduced the emulsification for 1000 cSt silicone oil (Siluron 2000) and for 1000 cSt silicone oil with an admixture of F6H8 (Densiron 68 HV).
New low-viscosity silicone oils show a reduced emulsification similar to that of 5000 cSt oils. In future, it may be possible to avoid using 5000 cSt oils. The findings may foster silicone oil surgery in general, and in particular the application of small-incision techniques.
Silicone oil; polydimethylsiloxane; emulsification; vitreous; treatment surgery
Scleritis is a potentially blinding inflammatory disorder. Standard care consists of systemic corticosteroids and immunosuppresants. The authors describe a series of 10 patients suffering from scleritis treated with the TNF inhibitor infliximab because this scleritis was refractory to standard therapy.
The authors reviewed the medical records of patients with scleritis at the Massachusetts Eye Research and Surgery Institution, treated with infliximab. All cases had non-infectious scleritis refractory to traditional immunomodulatory therapy and received 5 mg/kg of infliximab at 4–8-weekly intervals. The main outcome measures evaluated were clinical response, reduction in concomitant immunomodulatory therapy and adverse effects. Inflammation control and visual acuity were assessed using life-table methods.
A favourable clinical response to infliximab was seen in 100% of the patients, with six (60%) of them achieving remission and cessation of concomitant immunosuppression. A clinical response to infliximab therapy occurred within 13.24 weeks on average. Based on clinical response, the authors found that repeat monthly infusions were required to maintain remission. One (10%) patient developed a lupus-like reaction necessitating discontinuation of infliximab.
Infliximab may be considered in the treatment of non-infectious scleritis refractory to other treatment.
Episclera; sclera; infliximab; ocular inflammation; scleritis
To compare 1-year follow-up results of photorefractive keratectomy (PRK) with mitomycin C (MMC) and laser in situ keratomileusis (LASIK) for custom correction of myopia.
Eighty-eight eyes of 44 patients with moderate myopia were randomised to PRK with 0.002% MMC for 1 min in one eye and LASIK in the fellow eye. The 1-year follow-up was evaluated.
There were no differences between LASIK and MMC-PRK eyes preoperatively. Forty-two patients completed the 1-year follow-up. MMC-PRK eyes achieved better uncorrected visual acuity (p = 0.03) and better best-spectacle-corrected visual acuity (p<0.001) 1 year after surgery. SE did not differ in the two groups during follow-up (p = 0.12). Clinically significant haze was not found in surface ablation eyes. LASIK eyes showed a greater higher-order aberration (p = 0.01) and lower contrast sensitivity (p<0.05) than MMC-PRK eyes postoperatively. Excellent vision was reported in 64% of LASIK and 74% of MMC-PRK eyes 1 year after surgery. The corneal resistance factor and corneal hysteresis (ORA, Reichert) were higher in LASIK than in MMC-PRK eyes (p<0.01) at the last follow-up.
Wavefront-guided PRK with 0.002% MMC was more effective than wavefront-guided LASIK for correction of moderate myopia. Further research is necessary to determine the optimal concentration, exposure time and long-term corneal side effect of MMC.
To investigate the incidence of Nd:YAG-laser treatment for posterior capsular opacification (PCO) over a period of 5 years from phacoemulsification in an unselected population, comparing outcomes for three acrylic intraocular lenses (IOLs).
Retrospective longitudinal cohort study comprising 900 eyes. Three subgroups of 300 eyes, receiving the AR40, AR40e (Abbott Medical Optics, Santa Ana, California), or BL27 (Bausch & Lomb, Rochester, New York) IOL respectively, were compared. Data on patient age, gender, IOL type, dates of cataract surgery, Nd:YAG-laser treatment and/or death, and visual acuities before/after cataract surgery/Nd:YAG-laser treatment were collected from five sources: cataract operation register, patient administration system, quality control system for cataract operations, Nd:YAG-laser treatment register and clinical patient records.
216 eyes (24%) received Nd:YAG-laser treatment over a 5-year period. Statistically significant differences (p<0.001, χ2 test) were found between treatment rates for the three IOLs: AR40 73 eyes (24%), BL27 91 eyes (30%) and AR40e 52 eyes (17%). Eyes of patients who died during the follow-up period had fewer treatments (23/266, 8.6%) than eyes of patients living (193/634, 30%) at the end of the follow-up period.
In comparison with a hydrophobic acrylic IOL with sharp posterior optic edge, a hydrophilic acrylic IOL was associated with almost twice the number of Nd:YAG-laser treatments over the 5-year period. The results are useful for discussing the economic long-term consequences of choosing an IOL with a design that makes PCO development more or less likely. Caution is advised when applying data from post-mortem PCO studies on living populations.
Posterior capsular opacification; phacoemulsification; Nd-YAG lasers; longitudinal survey; retrospective study
To characterize new clinical features in a family with enhanced S-cone syndrome (ESCS) and investigate the pathogenesis of these clinical features in the homozygous Nr2e3rd7rd7 (rd7) mutant mice.
Four patients from an affected family were included for genotypic and phenotypic study. Eye tissues from rd7 mice were used to detect a possible relationship between macrophages and autofluorescent material by immunohistochemistry (IHC) staining.
Homozygous mutation in R311Q in NR2E3 was detected in this family. Color photographs revealed that white dots do not correlate to hyperautofluorescent spots seen in autofluorescence imaging of the macula. OCT showed rosette-like lesions similar to those found in rd7 mice histology sections. From IHC analysis, we observed that F4/80 (a pan macrophage marker), and autofluorescence were co-localized to the same cells within the retina rosettes.
Retinal structure of a young ESCS patient with homozygous R311Q mutation in the NR2E3 gene is similar to that seen in the rd7 mice. The macrophages were found to contain autofluorescent materials in the retinal rosettes of rd7 mice. Our data are consistent with macrophage infiltration contributing to the hyper-autofluorescent spots found in our patients.
photoreceptors; retinal degeneration; macrophages; A2E compound; lipofuscin
To evaluate the efficacy and safety of replacing latanoprost with another prostaglandin analogue (PGA) in patients with glaucoma or ocular hypertension requiring additional intraocular pressure (IOP) lowering while on latanoprost.
Prospective, randomised, investigator-masked, multicentre clinical trial. Patients on latanoprost 0.005% monotherapy requiring additional IOP lowering discontinued latanoprost and were randomised to bimatoprost 0.03% (n = 131) or travoprost 0.004% (n = 135). IOP was measured at latanoprost-treated baseline and after 1 month and 3 months of replacement therapy.
Baseline mean diurnal IOP on latanoprost was similar between groups. The mean diurnal IOP was significantly lower with bimatoprost than with travoprost at 1 month (p = 0.009) and 3 months (p = 0.024). Overall, 22.0% of bimatoprost patients versus 12.1% of travoprost patients achieved a ⩾15% reduction in diurnal IOP from latanoprost-treated baseline at both months 1 and 3 (p = 0.033). At month 3, the additional mean diurnal IOP reduction from latanoprost-treated baseline was 2.1 (95% CI 1.7 to 2.5) mm Hg (11.0%) with bimatoprost and 1.4 (95% CI 0.9 to 1.8) mm Hg (7.4%) with travoprost (p = 0.024). At 3 months, 11.5% of bimatoprost and 16.5% of travoprost patients demonstrated a ⩾1-grade increase in physician-graded conjunctival hyperaemia (p = 0.288). Hyperaemia was reported as a treatment-related adverse event in 3.1% of bimatoprost and 1.5% of travoprost patients (p = 0.445).
Patients on latanoprost requiring lower IOP achieved a greater additional short-term diurnal IOP reduction when latanoprost was replaced by bimatoprost compared with travoprost. Low rates of hyperaemia were observed in patients treated with bimatoprost or travoprost after switching from latanoprost.
This study was performed to independently assess the turnover rates of aqueous and lipid layers of the tear film.
Two fluorescent dyes, fluorescein sodium and 5-dodecanoylaminofluorescein (DAF), which is a free-fatty-acid conjugate of fluorescein, were applied to the right eye of 12 healthy volunteers. Fluorescent intensity of the precorneal tear film was measured at the central cornea every minute for 10 min for fluorescein sodium, and every 5 min for 50 min for DAF. The turnover rate was calculated by plotting fluorescent intensity against time in a semilog plot and expressed as %/min.
Turnover rates of fluorescein sodium and DAF were 10.3 (SD 3.7)%/min and 0.93 (0.36)%/min, respectively. The turnover rate of DAF was significantly lower than that of fluorescein sodium (p<0.05, Mann–Whitney test). The turnover rate of DAF positively correlated with that of fluorescein sodium (r = 0.93, p<0.05).
Our results indicate that the turnover of lipids in tears is much slower than the aqueous flow of tears, and that this lipid turnover is associated with the aqueous flow of tears in healthy adults.
An epidemiological study carried out in 2006 indicated a high prevalence of blinding trachoma in the Kolofata Health District, Far North Region, Republic of Cameroon. As a result, the national blindness control programme of Cameroon instituted a trachoma elimination programme using the SAFE strategy.
A campaign to treat the entire district population with azithromycin 1.5% eye drops was undertaken in February 2008. To measure the effectiveness of treatment on the prevalence of active trachoma, two epidemiological studies were conducted on a representative sample of children aged between 1 and 10 years. The first study was performed just prior to the treatment campaign and the second study was performed 1 year later.
The prevalence of active forms of trachoma (trachomatous inflammation—follicular (TF) + TF/trachomatous inflammation—intense (TI)) dropped from 31.5 (95% CI 26.4 to 37.5)% before treatment to 6.3 (95% CI 4.1 to 9.6)% 1 year after treatment—a reduction of nearly 80%. There were no reports of serious or systemic side effects. Tolerance was excellent and no treatment was interrupted.
Mass treatment with azithromycin 1.5% eye drops is feasible, well tolerated and effective.
To evaluate the long-term outcome of autologous graft of retinal pigment epithelium (RPE) in patients with geographic atrophy.
Ten patients with progressive geographic atrophy underwent translocation of an autologous graft of RPE, Bruch membrane and choroid. The visual acuity (VA), reading performance, microperimetry, optical coherence tomography (OCT), fundus autofluorescence, fluorescein angiography and indocyanine green angiography were assessed.
No recurrence of RPE atrophy was seen. All but one transplant were revascularised. Vascularisation persisted throughout the 3 years' follow-up. Spectral-domain OCT in some cases showed intact photoreceptors or intact outer nuclear and outer plexiform layer overlying the graft. In three cases, the grafts were positioned eccentrically; these patients did not benefit from surgery. The mean VA decreased from 20/80 (range: 20/800 to 20/40) at baseline to 20/200 (range: perception of hand movements to 20/32) at last follow-up. In two patients, VA were stable from 20/50 to 20/32 and 20/40 at the last follow-up, respectively. Postoperative complications included retinal detachment due to proliferative vitreoretinopathy, macular pucker, iritis, branch retinal vein occlusion and secondary ocular hypertension.
Some patients benefit for at least 3 years from a functioning RPE-choroid graft. Functional outcome in most patients, however, was limited due to complications and unfavourable patient selection.
Age-related macular degeneration; geographic atrophy; retinal pigment epithelium; treatment surgery; retina; macula; choroid