Matias Iglicki

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.

ANATOMICAL AND FUNCTIONAL OUTCOMES OF SYMPTOMATIC IDIOPATHIC VITREOMACULAR TRACTION: A Natural History Study From the Pan American Collaborative Retina Study Group

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 &mgr;m to 323 ± 121 &mgr;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.

Biomarkers and predictors for functional and anatomic outcomes for small gauge pars plana vitrectomy and peeling of the internal limiting membrane in naïve diabetic macular edema: The VITAL Study

Purpose We aimed to investigate biomarkers and predictive factors for visual and anatomical outcome in patients with naïve diabetic macular edema (DME) who underwent small gauge pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling as a first line treatment. Design Multicenter, retrospective, interventional study. Participants 120 eyes from 120 patients with naïve DME treated with PPV and ILM peeling with a follow up of 24 months. Methods Change in baseline best corrected visual acuity (BCVA) and central subfoveal thickness (CST) 1, 6, 12 and 24 months after surgery. Predictive value of baseline BCVA, CST, optical coherence tomography (OCT) features (presence of subretinal fluid (SRF) and photoreceptor damage), and time between DME diagnosis and surgery. Additional treatment for DME needed. Intra- and post-operative complications (cataract rate formation, increased intraocular pressure). Main outcome measures The correlation between baseline characteristics and BCVA response (mean change from baseline; categorized improvement ≥5 or ≥10; Early Treatment Diabetic Retinopathy Study (ETDRS) letters) 12 and 24 months after surgery. Results Mean BCVA was 0.66 ± 0.14 logMAR, 0.52 ± 0.21 logMAR, and 0.53 ± 0.21 logMAR (p<0.001) at baseline, 12 and 24 months, respectively. Shorter time from DME diagnosis until PPV (OR: 0.98, 95% CI: 0.97–0.99, p<0.001) was a predictor for good functional treatment response (area under the curve 0.828). For every day PPV is postponed, the patient’s chances to gain ≥5 letters at 24 months decrease by 1.8%. Presence of SRF was identified as an anatomical predictor of a better visual outcome, (OR: 6.29, 95% CI: 1.16–34.08, p = 0.033). Safety profile was acceptable. Conclusions Our results reveal a significant functional and anatomical improvement of DME 24 months after primary PPV, without the need for additional treatment. Early surgical intervention and presence of SRF predict good visual outcome. These biomarkers should be considered when treatment is chosen.

Long-term visual outcome and its predictors in macular oedema secondary to retinal vein occlusion treated with dexamethasone implant

Background To evaluate the functional long-term outcome in patients with macular oedema (MO) secondary to central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO) treated with dexamethasone implant (DEX implant) and to identify its clinical predictors. Methods A 24-month, retrospective, multinational, real-world study. Chart review of patients with either naïve or recurrent MO secondary to CRVO/BRVO treated with DEX implant, including best-corrected visual acuity (BCVA), central subfield thickness (CST), demographic baseline characteristics and details of any additional treatment during follow-up. Results A total of 155 eyes (65 CRVO, 90 BRVO) from 155 patients were included. At 24 months, mean BCVA did not change significantly in CRVO (−2.1±24.5 letters, p=0.96) and BRVO patients (1.3±27.0 letters, p=0.07). A worse baseline BCVA (p<0.001), visual acuity (VA) gain ≥5 letters at 2 months (p=0.006) and no need for adjunctive intravitreal therapy after first DEX implant (p=0.001) were associated with a better final BCVA gain. Treatment-naïve patients (p=0.006, OR: 0.25, 95% CI 0.11 to 0.57) and those with a baseline CST≤400 µm (p=0.02, OR: 0.25, 95% CI 0.10 to 0.63) were identified as being less likely to need additional intravitreal therapy. Conclusion Clinical baseline characteristics and the early treatment response were identified as possible predictors for long-term outcome and the need of adjunctive intravitreal therapy in MO secondary to BRVO/CRVO treated by DEX implant.