Long-term efficacy and safety of XEN-45 gel stent implantation in patients with normal-tension glaucoma.

BACKGROUND: Minimally invasive bleb surgery using the XEN-45 gel stent has not been established for the treatment of normal-tension glaucoma (NTG). The main objective of this study was to evaluate the long-term treatment efficacy and safety of XEN-45 in eyes with uncontrolled NTG. METHODS: A retrospective analysis of patients with NTG who underwent XEN-45 gel stent implantation at university hospital Tuebingen between 2016 and 2021. The primary outcome measure was surgical success after three years defined as lowering of intraocular pressure (IOP) of ≥ 20%, with target IOP between 6 and 15 mmHg. Success was complete without and qualified irrespective of topical antiglaucoma medication use. The need for further glaucoma surgery, except for needling, was regarded as a failure. The secondary outcome measures included changes in mean IOP, number of antiglaucoma medications, and needling and complication rates. RESULTS: Twenty-eight eyes from 23 patients were included in the final analysis. Complete and qualified success rates were 56.5% and 75% after three years, respectively. Mean postoperative IOP ± standard deviation decreased significantly after three years from 19.3 ± 2.0 mmHg at baseline to 13.7 ± 4.2 mmHg (n = 22; p < 0.0001). The median number of antiglaucoma medications decreased from 2 (range 0-4) to 0 after three years (range 0-3; p < 0.0001). Sixteen eyes (57%) required a median of 1 (range 1-3) needling procedures. One eye required further glaucoma surgery. No sight-threatening complications were observed. CONCLUSION: The XEN-45 stent is effective and safe for the long-term treatment of NTG. However, needling was frequently required to improve outcomes.

The time course of spontaneous closure of idiopathic full-thickness macular holes.

PURPOSE: Spontaneous closure of idiopathic full-thickness macular holes (iFTMH) has been reported regularly. However, little is known about its probability and timeline. METHODS: In this retrospective study all consecutive patients who presented between August 2008 and August 2019 were screened for the presence of a macular hole and only iFTMHs were included. The primary outcome measure was the spontaneous closure of the iFTMH. RESULTS: Of 1256 eyes with macular holes, 338 fulfilled the inclusion criteria. Spontaneous closure of the iFTMH was detected in 31 eyes (9.2%) with a median time of 44 days after diagnosis. Eyes exhibiting spontaneous closure demonstrated a higher baseline best-corrected visual-acuity (BCVA) and smaller iFTMH diameter (p < 0.0001 and p < 0.0001, respectively). The mean BCVA improved from 0.4 logMAR (SD ± 0.21) to 0.29 logMAR (SD ± 0.20) after spontaneous closure (p = 0.031). The iFTMH diameter was positively correlated with the time to spontaneous closure (Pearson-r = 0.37, p = 0.0377). Spontaneously closed iFTMHs reopened in 16% (n = 5) of cases, with a median of 136 days after closure. A logistic regression model showed the hole diameter was associated with spontaneous closure (odds-Ratio 0.97, 95%CI [0.96, 0.98]). The Kaplan-Meier-Curve revealed that approximately 25% of small-iFTMH (n = 124) and 55% of iFTMH with a diameter < 150µm (n = 48) closed spontaneously within two months. CONCLUSION: The established gold-standard for the treatment of iFTMHs is macular surgery. However, the potential for spontaneous closure of small iFTMHs must be acknowledged. Therefore, if surgical treatment is delayed in individual cases, close observation is recommended.

Interpretable detection of epiretinal membrane from optical coherence tomography with deep neural networks.

This study aimed to automatically detect epiretinal membranes (ERM) in various OCT-scans of the central and paracentral macula region and classify them by size using deep-neural-networks (DNNs). To this end, 11,061 OCT-images were included and graded according to the presence of an ERM and its size (small 100-1000 µm, large > 1000 µm). The data set was divided into training, validation and test sets (75%, 10%, 15% of the data, respectively). An ensemble of DNNs was trained and saliency maps were generated using Guided-Backprob. OCT-scans were also transformed into a one-dimensional-value using t-SNE analysis. The DNNs' receiver-operating-characteristics on the test set showed a high performance for no-ERM, small-ERM and large-ERM cases (AUC: 0.99, 0.92, 0.99, respectively; 3-way accuracy: 89%), with small-ERMs being the most difficult ones to detect. t-SNE analysis sorted cases by size and, in particular, revealed increased classification uncertainty at the transitions between groups. Saliency maps reliably highlighted ERM, regardless of the presence of other OCT features (i.e. retinal-thickening, intraretinal pseudo-cysts, epiretinal-proliferation) and entities such as ERM-retinoschisis, macular-pseudohole and lamellar-macular-hole. This study showed therefore that DNNs can reliably detect and grade ERMs according to their size not only in the fovea but also in the paracentral region. This is also achieved in cases of hard-to-detect, small-ERMs. In addition, the generated saliency maps can be used to highlight small-ERMs that might otherwise be missed. The proposed model could be used for screening-programs or decision-support-systems in the future.

Histopathological findings of failed blebs after microinvasive bleb surgery with the XEN Gel Stent and Preserflo MicroShunt.

PURPOSE: The success of XEN Gel Stent (XEN) and Preserflo MicroShunt (Preserflo) implantation depends mainly on the development of bleb fibrosis. This study aimed to describe the histological findings of bleb fibrosis after XEN and Preserflo surgery. METHODS: This retrospective study included patients with different types of glaucoma who underwent revision surgery after XEN or Preserflo implantation. The available clinical information and histological samples of removed fibrotic tissue were analyzed. RESULTS: Thirty-six patients were included. Revision surgery was performed at a median of 195 (range = 31-1264) days after primary surgery. The mean intraocular pressure changed from 29.1 (± 10.3) mmHg at baseline to 18.3 (± 8.7) mmHg (- 37%; p < 0.0001) and 16.2 (± 4.2) mmHg (- 45%; p < 0.0001) after 6 and 12 months, respectively. Histological analysis revealed an increase in activated fibroblasts and macrophages in all specimens and a parallel orientation of fibroblasts in a minor part of the probe in 60% of the specimens. No pronounced inflammatory reaction in the form of lymphocytic or granulocytic infiltration was observed. The comparison of specimens from uveitic glaucoma and primary open-angle glaucoma patients revealed no significant differences. CONCLUSIONS: The histological analysis of fibrotic blebs from the XEN and Preserflo implants did not show any pronounced immune or foreign-body reaction and revealed a similar histological pattern of failed blebs after trabeculectomy.

A Comparative Analysis of Traumatic Retinal Detachment After Open and Closed Globe Injuries in Children.

PURPOSE: Pediatric traumatic retinal detachment (RD) resulting from open globe (OGI) or closed globe injuries (CGI) presents unique challenges due to complexity often resulting in lifelong sequelae. This study compares pediatric traumatic RD outcomes and prognostic factors following OGI and CGI. METHODS: A retrospective analysis reviewed 47 cases of pediatric traumatic RD cases (age <18 years) undergoing retinal detachment surgery between 2002 and 2021. Among them, 25 cases were caused by CGI and 22 cases by OGI. Demographics, retinal detachment characteristics, surgical procedures, anatomical and functional results were assessed. Predictive factors for visual outcomes were investigated. RESULTS: In the CGI group, mean (± standard deviation) age was 11 ± 4 years, and 10 ± 5 years in the OGI group. CGI traumatic RD had significantly better preoperative (CGI: logMAR 1.39 ± 0.19 (mean ± standard error); OGI: logMAR 2.12 ± 0.20) and follow-up (CGI: logMAR 0.94 ± 0.19; OGI: logMAR 1.85 ± 0.20) best corrected visual acuity (BCVA) (p<0.05). Initial BCVA improvement was observed in CGI only. In multivariable analysis, prognostic factors for favorable BCVA outcomes included higher preoperative BCVA, older age and absence of proliferative vitreoretinopathy (p<0.05). CONCLUSION: Visual prognosis for pediatric traumatic RD remains limited, favoring CGI cases compared to OGI. Baseline BCVA emerged as major determinant of final visual acuity. Tailored management approaches can optimize treatment results.

Introducing a customized low-cost macular buckle.

PURPOSE: To demonstrate a novel surgical technique that is a low-cost alternative to commercial implants for macular buckling in high myopia. METHODS: A silicon encircling band serves as the anchor. A second silicon circling band is employed, with a 10mm silicon strip to widen the posterior scleral indentation. This band is inserted posteriorly the lateral and inferior rectus muscles and pushed behind the globe, orienting it in a superior-temporal to inferio-nasal position with the silicone strip directly under the macula. For better visualization, the placement of the macular buckle is done under the microscope. RESULTS: The placement of the macular buckle led to reattachment of the central retina in treated patients during long-term follow-up. This technique eliminates the need for detaching a rectus muscle. Visual acuity remained stable throughout the follow-up period. CONCLUSION: This customized macular buckle technique can improve the anatomical outcome in patients with central retinal detachment due to high myopia.

Restoring vision after cat bite: a case report on successful diagnostic and therapeutic regimen for Capnocytophaga endophthalmitis.

BACKGROUND: Capnocytophaga is a bacterium frequently found in the oral flora of dogs and cats (e.g. Capnocytophaga canimorsus) and humans (e.g. Capnocytophaga gingivalis). Among Capnocytophaga related ocular infections, fulminant endophthalmitis is a rare but sight-threatening clinical manifestation. CASE PRESENTATION: A 35-year-old previously healthy patient presented after a cat bite into the left upper and lower eyelid and nasal part of the conjunctiva of the left eye. At initial consultation, the corrected visual acuity was 0.8 in decimal scale and a detailed clinical examination revealed no evidence of ocular penetration. However, daily follow-up examinations under local therapy revealed a progressive intraocular inflammation, therefore the decision was made to perform a diagnostic vitrectomy with intravitreal and systemic antibiotic treatment. Capnocytophaga felis was detected as the cause of endophthalmitis and the initiated treatment resulted in quick morphological and functional recovery of the left eye. After surgery of secondary cataract, visual acuity improved from hand motion preoperatively to 1.0 postoperatively. CONCLUSIONS: Early recognition as well as prompt and effective treatment of animal bite associated endophthalmitis is essential for good visual recovery and functional outcome. Furthermore, this case highlights the importance of daily follow-up examinations, even in the absence of signs of ocular penetration and intraocular inflammation, to enable prompt and effective treatment initiation. Given the negative results in bacterial culture, we additionally emphasize the value of sequencing-based microbiological diagnostics in unclear cases.

Fall-related ocular trauma in patients over 90 years in tertiary ophthalmic center in Germany: 90-TOSG Report 1.

PURPOSE: To investigate the clinical characteristics of fall-related ocular trauma in patients over 90 years of age. METHODS: Retrospective, medical record reviews. Patients over the age of 90 years treated in a tertiary center with fall-related ocular trauma were included in the study. RESULTS: Fifty consecutive patients (fifty eyes) were analyzed. The mean age was 93.6 ± 1.8 years and 41 patients (82%) were female. The most common site of the injuries was orbital fracture (18 patients, 36%), accompanied with open globe rupture (OGR) in three patients, and globe contusion in two patients. Seventeen patients (34%) presented with OGR. Ocular trauma score in those patients was category 1 in 10 patients (58.8%) and category 2 in the others. Conjunctival hemorrhage and/or periocular contusion was seen in 14 patients (28%) and globe contusion in six patients (12%). At the presentation, the mean best corrected visual acuity (BCVA) was 2.82 ± 0.24 logMAR in patients with OGR and 1.98 ± 0.81 logMAR in six patients with globe contusion. Three of the patients with OGR had a final vision of 20/200 or better whereas the remaining patients had hand movements or less. The most common risk factors were female gender (82%) and use of antihypertensive drugs (46%). CONCLUSION: Patients with OGR had a poor visual outcome despite the early treatment. It is important to raise public awareness about of the poor prognosis of ocular injuries due to falls in the elderly population in order to establish preventive measures.

New XEN63 Gel Stent Implantation in Open-Angle Glaucoma: A Two-Year Follow-Up Pilot Study.

Purpose: The XEN gel stent was developed to reduce the risks of filtration surgery by standardizing the outflow of aqueous humor into the subconjunctival space. Recently, a modified version of the XEN63 gel stent was introduced. The goal of this study was to assess its efficacy and safety. Methods: This is a prospective, nonrandomized, observational, consecutive case series study at a single tertiary centre. Patients with open-angle glaucoma with above target intraocular pressure (IOP) despite maximal tolerated medication were included. The primary outcome was a change of median IOP. Secondary outcomes included a change in the number of medications, complete success, needling and complication rates. Success was defined as a lowering of IOP > 20% from baseline and IOP ≤ 14 mmHg. Complete success indicated that the target IOP was reached without medications. Results: Six patients were included. The median IOP decreased from 35.5 mmHg (25.0-40.0 mmHg) at baseline to 11.5 mmHg (4.0-15.0 mmHg, p = 0.03), and median IOP-lowering medication was reduced from 4.0 (3.0-4.0) at baseline to 0 (0-1.0, p = 0.03) after two years. Five patients (83.0%) had a complete success after two years. Two patients (33.0%) required a needling procedure. Three patients (50.0%) required an intervention due to symptomatic hypotony within the first three weeks postoperatively. Hypotony resolved completely or was asymptomatic after three months. Conclusion: Our study demonstrated a statistically significant reduction in both IOP and number of IOP-lowering medications. Complications were well manageable and had no long-term sequelae.

Long-term outcomes of autologous platelet treatment for optic disc pit maculopathy.

PURPOSE: Optic disc pits (ODPs) are rare congenital cavitary abnormalities of the optic nerve head, which can lead to serous macular detachments. The aim of this study was to evaluate the long-term efficacy of pars plana vitrectomy (PPV) combined with autologous platelet concentrate (APC) for the treatment of optic disc pit maculopathy (ODP-M). METHODS: A retrospective analysis was performed on eleven eyes of ten patients with ODP-M, who received PPV combined with APC. Nine eyes operated primary, four of which had a repeat surgery also with injection of APC and two eyes underwent a rescue surgery, after they have been operated in another eye center without APC. Morphological and functional results were the main outcome parameters, determined by optical coherence tomography (OCT) and best-corrected visual acuity (BCVA), respectively. RESULTS: The mean duration of visual loss before surgery was 4.7 ± 3.89 months (range 0-12 months). The mean BCVA increased significantly from 0.82 ± 0.33 logMAR (range 0.4-1.3) preoperatively to 0.51 ± 0.36 logMAR (range 0-1.2) at the last examination (p = 0.0022). A significant morphological improvement was also noticed with decrease of the mean foveal thickness from 935.82 ± 248.48 µm (range 559-1400 µm) preoperatively to 226.45 ± 76.09 µm (range 110-344 µm) at the final examination (p < 0.0001). The patients were followed-up for a mean 65.36 ± 48.81 months (range 1-144 months). Two eyes developed postoperatively a retinal detachment. Cataract surgery was performed in 5 eyes during the follow-up period. CONCLUSION: Our study demonstrated that PPV with APC can improve functional and morphological outcomes, both as a primary and a rescue therapy, without any recurrence over a long follow-up period. To the best of our knowledge, this was the longest observation period regarding the use of APC in treatment of ODP-M.

VOLUMETRIC ANALYSIS OF LAMELLAR MACULAR HOLE: An Optical Coherence Tomography Study.

BACKGROUND: To investigate the cavity of lamellar macular holes (LMH-CV) by using volumetric analysis of optical coherence tomography images. METHODS: Single-center, retrospective, observational case series. The volume of the LMH-CV and epiretinal proliferation was determined. Best-corrected visual acuity, central macular thickness, maximum horizontal diameter and minimum horizontal diameter, and the presence of foveal bump and ellipsoid zone defect were noted. RESULTS: Forty-nine eyes of 46 patients (20 women) were included in the baseline analysis. The natural course group consisted of 25 patients (27 eyes) with a mean follow-up of 19.2 ± 15.7 months. The volume of LMH-CV was found to be a predictive factor for baseline best-corrected visual acuity (P = 0.038, ß-coefficient = 0.338, 95% CI: 0.275-8.893). Whereas no significant change at the last visit was observed in central macular thickness, minimum horizontal diameter, and maximum horizontal diameter, the LMH-CV and epiretinal proliferation volume increased significantly (P = 0.036, P < 0.001, respectively). Eyes with foveal bump had larger minimum horizontal diameter, maximum horizontal diameter, and LMH-CV volume (P = 0.008, P < 0.001, P = 0.024, respectively). Eyes with ellipsoid zone defect showed larger LMH-CV and epiretinal proliferation volume, but thinner central macular thickness (P = 0.038, P = 0.004, P = 0.012, respectively). CONCLUSION: Volumetric analysis of LMH-CV detects changes in the natural course of lamellar macular hole earlier than the measurement of horizontal diameters. Further studies will clarify whether volumetric analysis of the lamellar macular hole is useful as an additional biomarker in the management of lamellar macular hole.

Clinical and morphological characteristics of patients with idiopathic epiretinal membrane with foveal herniation.

PURPOSE: To analyse the clinical and morphological characteristics of eyes with idiopathic epiretinal membrane (iERM) and foveal herniation (FH). METHODS: Clinical findings and OCT features of patients with iERM and FH were retrospectively analysed. Primary outcome were changes of the best-corrected-visual-acuity (BCVA) and OCT features from baseline to the last visit. FH patients were divided into two groups based on herniated layers: ganglion cell complex (GCC)-group and sub-GCC-group. Surgical outcome was also assessed. RESULTS: In this study, 3882 patients with iERM were screened, of whom 51 (1.3%) were identified with FH. The GCC-group (n = 16) had a better baseline BCVA and thinner central foveal thickness (CFT) in comparison to the sub-GCC-group (n = 35) but without statistical significance (p = 0.330, p = 0.417, respectively). The postoperative BCVA-improvement was similar between the two groups (p = 0.280). Fibrillary surface changes were detected in 42/51 (82.3%) patients, significantly more often in the sub-GCC group (p = 0.020). The baseline BCVA was a predictive factor for the postoperative vision change. CONCLUSION: FH presents with a unique macular morphology in eyes with iERM. Affected eyes experience varying visual disturbances based on the involvement of the inner retinal layers in the foveal herniation. Macular surgery is successful in restoring vision, even though foveal morphology does not fully recover.

Legal obligation in the general population: face mask influence on endophthalmitis after intravitreal injection.

PURPOSE: To investigate whether compulsory face masking in public life changes the incidence or pattern of post-injection endophthalmitis (PIE). PATIENTS AND METHODS: All injections of bevacizumab, ranibizumab, aflibercept, dexamethasone or triamcinolone between 01/01/2015 and 12/31/2021 at the University Eye Clinic of Tuebingen were included in this retrospective analysis. The injection procedure itself was unchanged since 2015 and included the use of a sterile drape covering the head up to the shoulders which prevents airflow toward the eye. Furthermore, all staff wore a face mask and gloves at all times. The two study periods were defined by the introduction of a compulsory face masking rule in public life (01/01/2015 until 04/27/2020 vs. 04/28/2020 until 12/31/2021). RESULTS: A total of 83,543 injections were performed in the tertiary eye clinic, associated with a total of 20 PIE (0.024%, 1/4177 injections). Of these, thirteen PIE were documented during the pre-pandemic period (0.021%, 1/4773 injections) and seven PIE during the pandemic period (0.033%, 1/3071 injections). No significant difference in PIE risk was observed (p = 0.49), and there was no case of oral flora associated PIE. CONCLUSION: Although some potential confounders (wearing time, skin flora) could not be considered, there was no clear signal that the introduction of compulsory face masking in public life did alter the risk for PIE in our patient population. Three and six months after PIE, no difference in visual acuity was detectable between the two study periods.

Clinical characteristics of patients with epiretinal membrane-Foveoschisis.

PURPOSE: The purpose of this study is to investigate the clinical and morphological characteristics of epiretinal membrane (ERM)-Foveoschisis. METHODS: Medical charts of 2088 patients diagnosed with idiopathic ERM were screened and eyes with ERM-Foveoschisis were included. All eyes underwent a complete ophthalmological examination including spectral domain optical coherence tomography (SD-OCT). OCT features and best corrected visual acuity (BCVA) were analysed. ERM-Foveoschisis was defined as open, closed, elevated or flat based on the OCT features. Ellipsoidal zone (EZ) abnormality, intraretinal cystoid spaces, central foveal thickness (CFT), posterior vitreous detachment (PVD) and lens status were assessed. RESULTS: One hundred-sixty-six patients (175 eyes) (72% female, mean age 70.46 years) were included. Incidence of ERM-Foveoschisis was 6.7%. Open type was seen in 86.8% and had a significantly better mean BCVA than closed type (p = 0.01). No statistically significant difference of mean BCVA was noted between the elevated and flat types. Mean BCVA was significantly lower in eyes with EZ abnormality (p = 0.03) and eyes with intraretinal cystoid spaces (p = 0.02). Patients with 'closed' ERM-Foveoschisis showed a significant higher median CFT than 'open' ERM-Foveoschisis (respectively, 364 µm and 176 µm, p < 0.001). A total of 81.9% eyes had PVD. CONCLUSION: We differentiated four morphological types of ERM-Foveoschisis based on the OCT examination. Closed ERM-Foveoschisis presented with a higher CFT and lower BCVA than the open type. ERM-Foveoschisis with cystoid intraretinal spaces presented with a lower BCVA. The impact of the morphological types of the ERM-Foveoschisis on the clinical course and for therapy decision requires further long-term studies.

Natural Course of Optic Disc Pit Maculopathy: An Optical Coherence Tomography Study.

PURPOSE: The aim of this study was to analyze the impact of OCT characteristics on the natural course of optic disc pit maculopathy (ODP-M). METHODS: This was a single-center, retrospective, observational case series. Patients with ODP-M were included in the study. Baseline demographic characteristics, central macular thickness (CMT), IPP, subretinal fluid (SRF), subretinal precipitations, outer retinal fluid (ORF), and outer retinal layer hole were evaluated. The changes in the OCT characteristics were analyzed with respect to the best-corrected visual acuity (BCVA) from baseline to the last visit. RESULTS: Twenty-two eyes of 22 patients were evaluated with a mean follow-up time of 37.6 (median 22) months. The mean BCVA was 0.31 logMAR at baseline and 0.28 logMAR at the final visit (p = 0.521). Baseline BCVA was significantly related to CMT (ß coefficient 0.001, p = 0.002). Mean BCVA increased in 7 patients (group 1), remained stable in nine (group 2), and decreased (group 3) in 6 patients. No significant difference was found between the groups regarding the baseline BCVA, CMT, and extent of retinal fluid. In patients with subretinal deposits, BCVA remained stable in 3 patients and worsened in one. ORF was recorded in all patients. In patients with SRF, the mean change of BCVA during follow-up differed significantly, depending on the presence (0.07 logMAR) or absence (-0.125 logMAR) of SRF (p = 0.019). CONCLUSION: Among the OCT characteristics, SRF was a negative prognostic factor in ODP-M. Most ODP-M patients showed improved or stable vision over 3 years of follow-up. Therefore, observation may be considered in patients with reasonable vision and without SRF even when they present with remarkable OCT findings.

Impact of OCT scan-patterns in identifying morphological features of lamellar macular holes and macular pseudoholes.

AIM: To evaluate the impact of the optical coherence tomography (OCT) scan patterns on the detection of the features associated with lamellar macular hole (LMH) and macular pseudohole (MPH). METHODS: This is a retrospective analysis of 100 consecutive eyes with LMH (n=41) and MPH (n=59) having at least three of the following OCT features, which include mandatory criteria for the diagnosis of LMH and MPH: Epiretinal membrane, epiretinal proliferation, verticalization, intraretinal cystoid spaces, foveoschisis, irregular foveal contour, foveal cavity with undermined edges, and ellipsoid line disruption. Primary outcome measurement was the detection frequency of the features in three different OCT scan patterns: 1) volume scan; 2) six radial scans (R6); and 3) vertical and horizontal radial scans (R2). RESULTS: Of the total eight features, the maximal detection frequency was found as 4.45±1.45, 4.35±1.47, and 3.70±1.59, by the volume, R6 and R2, respectively. R2 was inferior to the other patterns in detection of the total features (P<0.001), whereas R6 and volume patterns were found comparable (P=0.312). CONCLUSION: The physician should be aware that the selection of the OCT-scan pattern may influence the detection of mandatory morphological criteria for the diagnosis of LMH and MPH.

GUCY2D-Related Retinal Dystrophy with Autosomal Dominant Inheritance-A Multicenter Case Series and Review of Reported Data.

To report the clinical phenotype and associated genotype of a European patient cohort with GUCY2D-related autosomal-dominant (AD) cone-/cone-rod dystrophy (COD/CORD), we retrospectively analyzed 25 patients (17 female, range 12-68) with GUCY2D-related AD-COD/CORD from three major academic centers in Europe and reviewed the previously published data of 148 patients (visual acuity (VA), foveal thickness, age of first symptoms, and genetic variant). Considering all the patients, the onset of first symptoms was reported at a median age of 7 years (interquartile range 5-19 years, n = 78), and mainly consisted of reduced VA, photophobia and color vision abnormality. The disease showed a high degree of inter-eye symmetry in terms of VA (n = 165, Spearman's ρ = 0.85, p < 0.0001) and foveal thickness (Spearman's ρ = 0.96, n = 38, p < 0.0001). Disease progression was assessed by plotting VA as a function of age (n = 170). A linear best-fit analysis suggested a loss of 0.17 logMAR per decade (p < 0.0001). We analyzed the largest cohort described so far (n = 173), and found that the most common mutations were p.(Arg838Cys) and p.(Arg838His). Furthermore, the majority of patients suffered severe vision loss in adulthood, highlighting a window of opportunity for potential intervention. The emerging patterns revealed by this study may aid in designing prospective natural history studies to further define endpoints for future interventional trials.

Synthesis and Characterization of High-Performing Sulfur-Free Tannin Foams.

Tannin foams are green lightweight materials that have attracted industrial interest for the manufacturing of sandwich panels for insulation purposes. However, the dimensions of the cells and the presence of sulfur in the formulation developed until now have discouraged their upscaling. In this work, we present the synthesis and the characterization of the more promising small cell and sulfur-free materials. It was observed that, with respect to standard ones, foams catalyzed with nitric acid present similar physical properties and more phenolic character, which favors the absorption of ionic pollutants. Conversely, the foams blown with aliphatic solvents and surfactants present smaller pores, and higher mechanical and insulating properties, without affecting the chemical properties or the heating value. The combined foam produced with nitric acid as a catalyst and petroleum ether as a blowing agent result in sulfur-free and small cell material with overall improved features. These foams have been produced at 30 × 30 × 3 cm3, with high homogeneity and, to date, they represent the most suitable formulation for industrial upscaling.