characteristics of rod regeneration in a novel zebrafish retinal degeneration model using N-methyl-N-nitrosourea (MNU)

Primary loss of photoreceptors caused by diseases such as retinitis pigmentosa is one of the main causes of blindness worldwide. To study such diseases, rodent models of N-methyl-N-nitrosourea (MNU)-induced retinal degeneration are widely used. As zebrafish (Danio rerio) are a popular model system for visual research that offers persistent retinal neurogenesis throughout the lifetime and retinal regeneration after severe damage, we have established a novel MNU-induced model in this species. Histology with staining for apoptosis (TUNEL), proliferation (PCNA), activated Müller glial cells (GFAP), rods (rhodopsin) and cones (zpr-1) were performed. A characteristic sequence of retinal changes was found. First, apoptosis of rod photoreceptors occurred 3 days after MNU treatment and resulted in a loss of rod cells. Consequently, proliferation started in the inner nuclear layer (INL) with a maximum at day 8, whereas in the outer nuclear layer (ONL) a maximum was observed at day 15. The proliferation in the ONL persisted to the end of the follow-up (3 months), interestingly, without ongoing rod cell death. We demonstrate that rod degeneration is a sufficient trigger for the induction of Müller glial cell activation, even if only a minimal number of rod cells undergo cell death. In conclusion, the use of MNU is a simple and feasible model for rod photoreceptor degeneration in the zebrafish that offers new insights into rod regeneration

Artistic Practices: social interactions and cultural dynamics

This is the final version of the article. Available from the publisher via the link in this record.Book Review of: Zembylas, T. (Ed.). (2014). Artistic Practices: social interactions and cultural dynamics. Routledg

Causative Pathogens of Endophthalmitis after Intravitreal Anti-VEGF Injection: An International Multicenter Study

Purpose: The main objective of this study was to investigate the microbiological spectrum of endophthalmitis after anti- VEGF injections and to compare streptococcal with nonstreptococcus- associated cases with regard to baseline characteristics and injection procedure. Methods: Retrospective,international multicenter study of patients with culture-positive endophthalmitis after intravitreal anti-VEGF injection at 17 different retina referral centers. Results: Eighty-three cases with 87 identified pathogens were included. Coagulasenegative staphylococci (59%) and viridans streptococci (15%) were the most frequent pathogens found. The use of postoperative antibiotics and performance of injections in an operating room setting significantly reduced the rate of streptococcus-induced endophthalmitis cases (p = 0.01 for both). Conclusion: We found a statistically significant lower rate of postinjectional local antibiotic therapy and operating room-based procedures among the streptococcus-induced cases compared to cases caused by other organisms

Baseline predictors for visual acuity loss during observation in diabetic macular oedema with good baseline visual acuity

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Anatomical and functional outcomes of symptomatic idiopathic vitreomacular traction

Purpose: To describe the natural history of eyes with symptomatic idiopathic vitreomacular traction (VMT). Methods: Retrospective multicenter study of 168 eyes with spectral-domain optical coherence tomography (SD-OCT) findings consistent with idiopathic VMT. All eyes were graded according to SD-OCT findings. Grade 1 was defined as incomplete cortical vitreous separation with foveal attachment. Grade 2 was defined as Grade 1 plus intraretinal cysts or clefts. Grade 3 was defined as Grade 2 plus a foveal detachment. All patients were followed for at least 6 months. Results: There were 168 patients (51 men) with a mean age of 68.8 ± 10.7 years. Patients were followed for a mean of 22.7 ± 20.1 months. The mean duration of symptoms before the initial presentation was 3.65 ± 5.42 months. At baseline, 72 eyes had Grade 1, 74 eyes had Grade 2, and 22 eyes had Grade 3 SD-OCT findings. Over the follow-up period, 36 eyes (21.4%) had spontaneous resolution of the VMT with normalization of the foveal anatomy. The mean time to resolution was 12.3 ± 12.6 months. An unfavorable anatomical outcome occurred in 7.7% (13 of 168) of the eyes, with 6 eyes developing a lamellar macular hole and 7 eyes developing a full-thickness macular hole. This occurred at a mean of 10.3 ± 10.7 months after the presentation. Subgroup analysis based on baseline SD-OCT grade showed that 4.1% (3 of 73) of Grade 1 eyes compared with 6.8% (5 of 74) of Grade 2 eyes, and 23.8% (5 of 21) of Grade 3 eyes developed a full-thickness macular hole or lamellar macular hole (P 0.0109, chi-square test). In the remaining 119 eyes, at the last follow-up, 65 eyes had Grade 1, 42 eyes had Grade 2, and 12 eyes had Grade 3 VMT. On average, the best-corrected visual acuity improved from 0.40 ± 0.35 logarithm of the minimum angle of resolution (Snellen, 20/50) at baseline to 0.35 ± 0.36 logarithm of the minimum angle of resolution (Snellen, 20/45; P 0.0372), and the mean central macular thickness improved from 350 ± 132 m to 323 ± 121 m. Conclusion: Spontaneous resolution of VMT occurred in 21.4% (36 of 168) of eyes after a mean follow-up of 11.4 ± 12.6 months. An unfavorable anatomical outcome occurred in 7.7% (13 of 168) of eyes. The baseline SD-OCT grade may predict the progression to full-thickness macular hole

Half-Dose Photodynamic Therapy as a Novel Treatment Protocol for Circumscribed Choroidal Hemangioma

We present a case series of four patients with circumscribed choroidal hemangioma (CCH) treated with half-dose PDT, proposing this as a novel treatment protocol. Four patients with CCH were included, and then evaluated using multimodal imaging, including optical coherence tomography (OCT), fluorescein angiography, indocyanine green angiography, fundus autofluorescence, and ultrasound following treatment with half-dose and full-fluence PDT. Following half-dose PDT, all patients showed significant shrinkage of the hemangioma, functional improvement, and decrease of intra- and sub-retinal fluid. All patients remained stable after a single PDT treatment, with a follow-up of up to 60 months. No side effects were shown. This is the first report showing long term efficacy of half-dose PDT treatment in cases with CCH. The outcomes from this pilot study are comparable with results using full dose PDT protocols and it can be considered as a viable treatment option for CCH during the ongoing global verteporfin shortage

Polypoidal Lesions Associated with Choroidal Nevi

Purpose: To investigate eyes with polypoidal lesions associated with choroidal nevi, their multimodal imaging characteristics, and long clinical follow-up. Methods: Multicenter, retrospective case series study of patients with polypoidal lesions overlying choroidal nevi. Demographic and clinical information was recorded. Multimodal imaging including colour fundus photography (CFP), optical coherence tomography (OCT), OCT angiography, fundus fluorescein angiography (FA), indocyanine angiography (ICGA) and A- and B-scan ultrasonography were analyzed for nevus and polypoidal lesion characteristics. Results: Fourteen eyes (14 patients; mean age: 70.3±6.7 years) with polypoidal lesions overlying choroidal nevi were included. The mean follow-up duration was 50.0±27.9 months (range 12-108). All nevi were pigmented on CFP, flat on ultrasonography with a mean basal diameter of 3.8±0.4 mm. In all but one eye, OCT showed a shallow irregular pigment epithelium detachment (SIRE) overlying the nevus. A total of 11/14 eyes (78.6%) had exudative activity, 9 eyes received intravitreal anti-vascular endothelial growth factor (VEGF) injections, and one eye required intravitreal anti-VEGF combined with photodynamic therapy (PDT). Mean visual acuity was 20/32 at baseline and 20/50 at final visit. Conclusions: We present the largest known cohort of eyes with polypoidal lesions associated with choroidal nevi with up to 9 years follow-up. The exudative degree of the polypoidal lesion in this condition is variable and treatment decisions should be taken on an individual basis. We hypothesize that choroidal ischemia due to altered choroidal vasculature rather than Haller layer hyperpermeability plays a role in the formation of polypoidal lesions overlying nevi

Cell proliferation in the zebrafish retina exposed to 150 mg/l MNU.

<p>Proliferating cell nuclear antigen (PCNA) positive cells (white) indicate proliferation and were found in the ciliary marginal zone (CMZ) at all time points and in the untreated fish. Furthermore, PCNA-positive cells were observed in the inner nuclear layer (INL) starting at day 3 and their number was highest at day 8. Proliferating cells in the outer nuclear layer (ONL) were not found before day 5 but their number was highest at day 15. From day 30 on, nearly no proliferating cells were seen in the INL, whereas proliferation in the ONL occurred until the end of follow up at day 90. Scale bar indicates 100 μm.</p

Cell counts in different retinal layers for zebrafish exposed to MNU at baseline and follow-up.

<p>A. MNU 50 mg/l group: No relevant decrease in retinal cells was observed (p>0.05). B. MNU 150 mg/l group: Rod cell loss started at day 5; the number of rods was lowest at day 8 (p≤0.01) with a decrease of 79.6%, but fully recovered by day 60. Other retinal layers did not display any relevant decrease of cell numbers after MNU exposure (p>0.05). GC (ganglion cells), INL (inner nuclear layer), RN (rod nuclei) and CN (cone nuclei). Baseline values are defined as 100%. Mean values with SEM error bars are represented (* indicates p≤0.01 compared with day 0).</p