Reduction of lens size in PAX6-related aniridia.

Heterozygous mutation of PAX6 in humans leads to congenital aniridia (OMIM 106210) which is typified by congenital iris and foveal defects, and later onset glaucoma, aniridic keratopathy, and cataract. Mice heterozygous for Pax6 mutations phenocopy many aspects of aniridia including the iris defects, keratopathy and cataract, although Pax6 mutant mice have small lenses, a phenotype which is not typically reported in human aniridia, perhaps due to difficulties in measuring lens diameter during typical ophthalmic examinations as the lens periphery is shielded by the iris. In order to overcome this, records of patients diagnosed with congenital aniridia between April 2015 and May 2021 at the Necker-Enfants Malades Hospital, and genetically confirmed with a disease-causing PAX6 variant, were retrospectively reviewed for those with normal axial length whose iris defects allowed visualization of the lens margins and corneal diameter to allow calculation of a lens/corneal diameter ratio. This value was compared with values obtained from a cohort of patients with Sjödell grade IV oculocutaneous albinism type 1 (OCA1; OMIM 203100) which allowed visualization of the lens periphery via iris transillumination. This analysis revealed that patients with congenital aniridia had a significantly lower lens/corneal ratio when compared to those with albinism, suggesting that humans haploinsufficient for PAX6, like mice, rats, frogs, and zebrafish, exhibit reductions in lens size.

Optic Disc Hypoplasia Assessment in PAX6 -Related Aniridia.

BACKGROUND: This study aims to characterize optic disc hypoplasia in congenital aniridia using ultra-wide-field imaging (UWFI) and nonmydriatic retinal photography (NMRP). We also investigated the relation between optic disc hypoplasia and foveal hypoplasia. METHODS: This is a retrospective case series of patients diagnosed with PAX6 -related aniridia in a National Referral Center, who underwent UWFI, NMRP, and spectral-domain optical coherence tomography (SD-OCT) . The disc diameter (DD) and the disc-to-fovea distance (DF) were measured. The DD:DF ratio was used to assess the relative size of the optic disc. The analyses were carried with respect to paired age- and sex-matched healthy controls. SD-OCT was used for foveal hypoplasia grading (from 1 to 4) and retinal nerve fiber layer (RNFL) analysis. RESULTS: Mean manual DD:DF ratio was 0.33 (95% CI: 0.31-0.35) in aniridia patients versus 0.37 (95% CI: 0.36-0.39) in control patients (n = 20, P = 0.005) measured on NMRP and 0.32 (95% CI: 0.30-0.35) in aniridia patients versus 0.37 (95% CI: 0.37-0.39) in control patients (n = 26, P < 0.0001) when assessed on UWFI. Mean semiautomated DD:DF ratio measured on UWFI in aniridia patients was 0.31 (95% CI: 0.29-0.33) versus 0.37 (95% CI: 0.36-0.38) in control patients ( P < 0.0001). Also, a negative correlation was found significant between the grade of foveal hypoplasia and the mean semiautomated DD:DF ratio (r = -0.52, 95% CI: -0.76 to -0.15, P = 0.0067). Finally, a significant negative correlation was found between the peripapillary temporal RNFL thickness and the grade of foveal hypoplasia ( P = 0.0034). CONCLUSIONS: The DD:DF ratio is significantly reduced in PAX6 -related aniridia patients and correlates with the severity of foveal hypoplasia. This ratio is a valuable tool for optic disc hypoplasia assessment in congenital aniridia, especially when provided semiautomatically by UWFI.

In Vitro and In Vivo Safety of Hyaluronic Acid-Decorated Microparticles for Intravitreal Injection of Palmitoylethanolamide, Citicoline, or Glial-Cell-Derived Neurotrophic Factor.

The treatment of posterior eye segment diseases through intravitreal injection requires repeated injections of an active molecule, which may be associated with serious side effects and poor patient compliance. One brilliant strategy to overcome these issues is the use of drug-loaded microparticles for sustained release, aiming at reducing the frequency of injections. Therefore, the aim of this work was to assess the safety features of poly(lactic-co-glycolic acid) (PLGA)-based, hyaluronic acid-decorated microparticles loaded with palmitoylethanolamide (PEA), citicoline (CIT), or glial-cell-derived neurotrophic factor (GDNF). Microparticles were prepared by double emulsion-solvent evaporation and fully characterized for their technological features. Microparticles possessed a satisfactory safety profile in vitro on human retinal pigment epithelial (ARPE-19) cells. Interestingly, the administration of free GDNF led to a loss of cell viability, while GDNF sustained release displayed a positive effect in that regard. In vivo results confirmed the safety profile of both empty and loaded microparticles. Overall, the outcomes suggest that the produced microparticles are promising for improving the local administration of neuroprotective molecules. Further studies will be devoted to assess the therapeutic ability of microparticles.

The FLURESP European commission project: cost-effectiveness assessment of ten public health measures against influenza in Italy: is there an interest in COVID-19 pandemic?

BACKGROUND: The FLURESP project is a public health research funded by the European Commission, with the objective to design a methodological framework to assess the cost-effectiveness of existing public health measures against human influenza pandemics. A dataset has been specifically collected in the frame of the Italian health system. As most of interventions against human influenza are relavant against other respiratory diseases pandemics, potential interests in COVID-19 are discussed. METHODS: Ten public health measures against human influenza pandemics pandemic were selected to be also relevant to other respiratory virus pandemics such as COVID 19: individual (hand washing, using masks), border control (quarantine, fever screening, border closure), community infection (school closure, class dismissal, social distancing, limitation of public transport), reduction of secondary infections (implementation of antibiotic therapy guidelines), pneumococcal vaccination for at-risk people, development of Intensive Care Unit (ICU) capacity, implementation of life support equipments in ICU, screening interventions, vaccination programs targeting health professional and targeting general population. RESULTS: Using mortality reduction as effectiveness criteria, the most cost-effective strategies are "reduction of secondary infections" and "implementation of life support equipment in ICU". The least cost-effective option whatever the level of pandemic events are screening interventions and mass vaccination. CONCLUSIONS: A number of intervention strategies against human influenza pandemics appears relevant against every respiratory virus, including the COVID-19 event. Measures against pandemics should be considered according to their expected effectiveness but also their costs for the society because they impose substantial burden to the population, confirming the interest of considering cost-effectiveness of public health measures to enlighten decision making.

Retinopathy of prematurity detection: a retrospective quality improvement project before-after implementation of retinal digital imaging for screening.

Screening of retinopathy of prematurity (ROP) was modified in a level-3 neonatal intensive care unit by the introduction of a wide-field retinal imaging. The aim of this study was to evaluate whether retinopathy of prematurity (ROP) diagnosis was improved or not compared to previously used binocular indirect ophthalmoscopy (BIO). This was a retrospective, uncontrolled, quality improvement project. Records of consecutive premature newborns screened for ROP over two 1-year periods were reviewed. Systemic factors potentially influencing the occurrence of ROP were investigated using uni- and multivariable linear regression followed by stepwise forward regression. ROP screening was performed by ophthalmologists using BIO in 2014, and digital wide-field retinal imaging (Panocam™ pro) in 2019. Records of N = 297 patients were analyzed (N = 159 in 2014 and N = 138 in 2019). The proportion of ROP diagnosed at any stage, over the total number of neonates screened, was significantly higher in 2019 (n = 46/138, 33.1%) compared to 2014 (n = 11/159, 6.9%) (p < 0.0001). Most neonates presented with mild forms of ROP during both 1-year periods analyzed. After adjustment for all parameters influencing ROP occurrence, the variables contributing independently to the diagnosis of any stage of ROP were birth weight (p = 0.002), duration of mechanical ventilation (p = 0.028) and wide-field fundus camera-assisted screening (p < 0.001). CONCLUSION: After adjusting for many recognized systemic factors influencing the development of ROP, screening by wide-field digital retinal imaging was independently associated with higher ROP detection. WHAT IS KNOWN: • No consensus has been reached to replace binocular indirect ophthalmoscopy by retinal imaging for ROP screening. • Diagnostic accuracy and high sensitivity and specificity has been reported for wide-field digital imaging. WHAT IS NEW: • The introduction of wide-field imaging for ROP screening in at level-3 reference center was independently associated to higher ROP detection.

Study protocol of OmegaROP-2 prospective study: expression of placental fatty acid receptors in preterm newborns with retinopathy of prematurity.

BACKGROUND: Incomplete vascularization of the retina in preterm infants carries a risk of retinopathy of prematurity (ROP). Progress in neonatal resuscitation in developing countries has led to the survival of an increasing number of premature infants, resulting in an increased rate of ROP and consequently in visual disability. Strategies to reduce ROP involve optimizing oxygen saturation, nutrition, and normalizing factors such as insulin-like growth factor 1 and n-3 long-chain polyunsaturated fatty acids (LC-PUFA). Our previous study, OmegaROP, showed that there is an accumulation or retention of docosahexaenoic acid (DHA) in mothers of infants developing ROP, suggesting abnormalities in the LC-PUFA placental transfer via fatty acid transporting proteins. The present study aims to better understand the LC-PUFA transport dysfunction in the fetoplacental unit during pregnancy and to find a novel target for the prevention of ROP development. METHODS: The study protocol is designed to evaluate the correlation between the expression level of placental fatty acid receptors and ROP occurrence. This ongoing study will include 100 mother-infant dyads: mother-infant dyads born before 29 weeks of gestational age (GA) and mother-infant dyads with full-term pregnancies. Recruitment is planned over a period of 46 months. Maternal and cord blood samples as well as placental tissue samples will be taken following delivery. ROP screening will be performed using wide-field camera imaging according to the International Classification of ROP consensus statement. DISCUSSION: The results of this study will have a tangible impact on public health. Indeed, if we show a correlation between the expression level of placental omega-3 receptors and the occurrence of ROP, it would be an essential step in discovering novel pathophysiological mechanisms involved in this retinopathy. TRIAL REGISTRATION: NCT04819893.

EVIDENCE AGAINST A CONTRALATERAL COATS PHENOTYPE BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To evaluate the laterality of Coats disease by analyzing optical coherence tomography angiography features in affected, fellow, and control eyes. METHODS: Patients with Coats disease who underwent optical coherence tomography angiography were retrospectively reviewed. Healthy eyes of age-matched patients served as controls. Automated optical coherence tomography angiography determination of foveal avascular zone size and vascular density of superficial capillary plexus and deep capillary plexus was recorded. RESULTS: Thirty-four patients with Coats disease (13 with bilateral optical coherence tomography angiography) and 24 controls were included. The foveal avascular zone was larger in affected eyes compared with fellow eyes (P = 0.004). Vascular density was decreased in affected eyes compared with fellow eyes in the superficial capillary plexus and deep capillary plexus whole images (P = 0.047 and P = 0.007) and in the deep capillary plexus at the fovea (P = 0.001). Vascular density was significantly reduced only in the deep capillary plexus in Stage 1 or 2A patients but in both plexuses in patients with Stage 2B1. No differences were shown on foveal avascular zone and vascular density values between fellow eyes of patients with Coats disease and controls. CONCLUSION: The foveal avascular zone is enlarged, and vascular density is decreased in affected eyes with Coats disease, but no differences are seen between fellow and control eyes, confirming the unilateral nature of the disease.

APPLICATION OF MODIFIED NEI VFQ-25 AFTER RETINAL DETACHMENT TO VISION-RELATED QUALITY OF LIFE.

PURPOSE: We examined the postoperative visual recovery and quality of life after retinal detachment (RD) surgery. METHODS: In addition to a baseline clinical examination, patients filled out the National Eye Institute Visual Functioning Questionnaire at three time points: preoperatively and 1 and 3 months postoperatively (M1 and M3, respectively). We analyzed the composite score and short-form scores (socioemotional scale [SFSES] and visual functioning scale [SFVFS]). RESULTS: One hundred ninety-four patients were enrolled in this study; 47 (26 macula-ON RD and 21 macula-OFF RD) returned all three questionnaires. The best corrected visual acuity was Snellen equivalent 20/25, 20/25, and 20/20 at the preoperative, M1, and M3 assessment, respectively. At M3, we found a positive correlation between SFSES and best corrected visual acuity measures among macula-OFF patients (P < 0.001, R2 = 0.58). A significant correlation with the best corrected visual acuity among macula-ON patients was observed only at M3 with the SFVFS score (P < 0.001, R2 = 0.41). CONCLUSION: The quality of life differs between ON and OFF RD in regard to the composite score and especially SFSES and SFVFS. We found a transient decrease in the quality of life at M1 for macula-ON patients, whereas the quality of life improved throughout follow-up among macula-OFF patients. These data may help improve the management of patients' expectations after RD surgery.

Levels of the oxidative stress biomarker malondialdehyde in tears of patients with central serous chorioretinopathy relate to disease activity.

Purpose: Central serous chorioretinopathy (CSCR) has been associated with oxidative stress-related risk factors. The objective of this study was to optimize an analytical method for evaluating the oxidative stress biomarker malondialdehyde (MDA) in human tears and determine its level in the tears of patients with CSCR. Methods: In this pilot study, tear samples were obtained from 34 healthy donors and 31 treatment-naïve CSCR male patients (eight with acute CSCR and 23 with chronic CSCR). Two analytical methods based on high-performance liquid chromatography followed by fluorescence detection were evaluated, with either 2-thiobarbituric derivative (TBA) or 2-aminoacridone (2-AA). Activity of CSCR was defined by the serous retinal detachment (SRD) height, which was measured by two independent observers on spectral-domain optical coherence tomography. Results: The 2-AA method showed higher sensitivity and precision compared to the TBA method. When the 2-AA method was applied to tears from healthy donors, the levels of MDA were statistically significantly higher in men compared to women (mean ± standard deviation, SD: 9,914 nM ± 6,126 versus 4,635 nM ± 1,173, p = 0.006). No difference was found in tear MDA levels between male patients with CSCR and age-matched control men (p = 0.17). However, MDA levels were statistically significantly higher in acute compared to chronic CSCR cases (mean ± SD: 12,295 nM ± 8,495 versus 6,790 ± 3,969 nM, p = 0.03). Additionally, there was a correlation between MDA levels and RPE leakage, quantified by the height of the serous retinal detachment (p = 0.02, r = 0.40). Conclusions: Levels of MDA in tears, measured with an optimized analytical method, correlate with RPE leakage in CSCR.

CHANGES IN VISUAL ACUITY AND PHOTORECEPTOR DENSITY USING ADAPTIVE OPTICS AFTER RETINAL DETACHMENT REPAIR.

PURPOSE: To quantify changes in photoreceptor density using adaptive optics fundus camera in patients after retinal detachment (RD) and to correlate them with macular involvement and best-corrected visual acuity. METHODS: At 1 and 3 months (M1 and M3) after vitrectomy, 194 patients underwent adaptive optics imagery in both eyes, at 5 locations, that we matched between time points using anatomical landmarks. Twenty-two patients (10 fovea-OFF [OFF] and 12 fovea-ON [ON]) had matched and analyzable adaptive optics images. We used analysis of variance for repeated measures. RESULTS: Best-corrected visual acuity (logarithm of the minimum angle of resolution and Snellen equivalent [SE]) was significantly different between OFF and ON RDs at baseline: 2.0 (2.3-0.95) (SE: 20/2000) versus 0 (0.1-0) (SE: 20/20); at M1: 0.35 (0.5-0.1) (SE: 20/40) versus 0.05 (0-0.1) (SE: 20/25); and at M3: 0.25 (0.3-0.1) (SE: 20/32) versus 0 (0-0) (SE: 20/20). We observed that cone density was stable in fellow eyes between M1 and M3 (P = 0.67); decreased in treated eyes than in fellow eyes (P < 0.05); and increased postoperatively in the ON group (P = 0.02) but not in the OFF group (P = 0.97). Visual acuity and RD type were independently correlated with cone density (P = 0.004, P = 0.000). CONCLUSION: Postoperative cone density was reduced in OFF RD, but also in the ON group, although the drop recovered during the 3-month follow-up. Cone density was significantly correlated with both visual acuity and type of RD at both time points.

CENTRAL RETINAL VEIN OCCLUSION IN OTHERWISE HEALTHY CHILDREN AND ADOLESCENTS: Association With Multigenetic Variants of Thrombophilia.

PURPOSE: To report cases of central retinal vein occlusion in otherwise healthy children showing combined genetic variants of thrombophilia. METHODS: Ophthalmological, pediatric records and genetic analyses of thrombophilia-associated variants were retrospectively reviewed in four children diagnosed with central retinal vein occlusion. Genetic screening, including Factor XII, platelet glycoprotein (GP) IIIa PlA1/A2 (rs5918), and GPIa/IIa C807T (rs1126643) and G873A (rs1062535) mutations, was performed by PCR amplification and Sanger sequencing of PCR products. The genotyping of prothrombin G20210A, Leiden Factor V G1691A, methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C mutations, and plasminogen activator inhibitor-1 4G/5G polymorphisms was performed by real-time PCR with Fluorescence Resonance Energy Transfer (FRET) probes. RESULTS: The genotyping analysis identified combined genetic variants of thrombophilia in each patient. Mutations for MTHFR (C677T) and GPIIIa PlA1/A2 were detected in Case 1, mutations for MTHFR (C677T), GPIIIa PlA1/A2, and GPIa/IIa in Case 2, mutations for MTHFR (C677T) and GPIa/IIa in Case 3, and mutation for MTHFR (A12986C), GPIIIa Pl A1/A2, and GPIa/IIa in Case 4. Preventive low-dose aspirin therapy was prescribed to all patients. During a follow-up of 5 and 8 years, neither central retinal vein occlusion recurrence nor any other thrombotic event was observed in Cases 1 and 2, respectively. CONCLUSION: In otherwise healthy children presenting central retinal vein occlusion, genetic investigations for thrombophilia-associated variants should be considered, given the possible long-term benefit of aspirin prophylaxis.

EVOLUTION AND PATTERNS OF CHOROIDAL THICKNESS CHANGES IN RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To evaluate the changes in choroidal thickness (CT) before and after a successful pars plana vitrectomy for rhegmatogenous retinal detachment (RD), and to compare the evolution of CT with respect to the extent of RD. METHODS: Fifty-four patients were divided into three groups: peripheral macula-on RD (>3 mm from the fovea; 14 eyes); paracentral macula-on RD (fovea-sparing; ≤3 mm from the fovea; 14 eyes); and macula-off RD (involving the fovea; 26 eyes). Choroidal thickness was measured at 1 month (M1) and 3 months (M3) postoperatively, preoperatively in macula-on RDs, with enhanced depth imaging optical coherence tomography, from the nasal side (+2.5 mm) to the temporal side (-2.5 mm) of the fovea. RESULTS: In peripheral macula-on RD, the intereye difference in CTs showed thickening throughout follow-up (subfoveally: preoperatively = 19.6% ± 43.9%, M1 = 22.9% ± 27.5%, M3 = 18.2% ± 35.6%). In paracentral macula-on RD, the intereye difference in CTs showed a thinning throughout follow-up (subfoveally: preoperatively = -7.8% ± 21.9%, M1 =-5.5% ± 26.1%, M3 = -9.3% ± 19.4%), as well as in the macula-off RD (subfoveally: M1 = -14.1% ± 18.7%, M3 = -9.9% ± 15%). CONCLUSION: The extent of RD was related to the evolution of the CT before and after surgery. Further studies are necessary to clarify the relationship between the changes in CT and the effects of circulatory alterations, vitrectomy, and RD.

Pars plana vitrectomy under melphalan irrigation for recurrent retinal detachment in eyes treated for retinoblastoma: a case report.

BACKGROUND: Tractional retinal detachment with or without secondary tear is a rare complication reported in less than 0.5% of in eyes treated for retinoblastoma. Pars plana vitrectomy (PPV) in eyes with history of retinoblastoma has been associated with a significant risk for recurrence, extraocular spread, and systemic metastases. We report here the successful management by PPV under melphalan irrigation of 2 children presenting with tractional retinal detachment after retinoblastoma therapy and scleral buckle surgery. CASE PRESENTATION: A 7-year-old girl with a history of bilateral retinoblastoma (group D) presented with light perception best-corrected visual acuity (BCVA) and tractional retinal detachment (RD) in her left eye, 3 years after the last intra-arterial chemotherapy (IAC) injection. Moreover, she had history of left eye rhegmatogenous RD treated by scleral buckle 1 month after the last IAC and cataract surgery 12 months later. PPV associated with retinectomy, laser photocoagulation and silicone oil tamponade was performed. Silicone oil was removed 4 months later. Fifteen months after PPV, BCVA had increased to 20/32 without recurrence of RD and no evidence of tumor activity. A 7-year-old boy with a history of unilateral retinoblastoma (group D) in his left eye presented with rhegmatogenous RD 21 months after the last treatment for retinoblastoma. Scleral buckle surgery was performed, but 3 weeks later the patient presented with tractional RD associated with proliferative vitreo-retinopathy. BCVA was counting fingers. PPV associated with membrane peel, laser photocoagulation and silicone oil tamponade was performed. Silicone oil was removed after 5 months followed by cataract surgery 5 months later. Twenty months after PPV, BCVA was 20/20 and there was no sign of tumor recurrence. CONCLUSIONS: PPV under melphalan irrigation, with retinectomy, if necessary, and silicone oil tamponade, allows anatomical and functional improvement in eyes with history of retinoblastoma and scleral buckling developing tractional RD.

Review: The bile acids urso- and tauroursodeoxycholic acid as neuroprotective therapies in retinal disease.

Bile acids are produced in the liver and excreted into the intestine, where their main function is to participate in lipid digestion. Ursodeoxycholic acid (UDCA) and tauroursodeoxycholic acid (TUDCA) have shown antiapoptotic, anti-inflammatory, and antioxidant effects in various models of neurodegenerative diseases. However, little is known about signaling pathways and molecular mechanisms through which these bile acids act as neuroprotectors, delaying translation to the clinical setting. We review evidence supporting a potentially therapeutic role for bile acids in retinal disorders, and the mechanisms and pathways involved in the cytoprotective effects of bile acids from the liver and the enterohepatic circulation to the central nervous system and the retina. As secondary bile acids are generated by the microbiota metabolism, bile acids might be a link between neurodegenerative retinal diseases and microbiota.

Mineralocorticoid antagonists in the treatment of central serous chorioetinopathy: Review of the pre-clinical and clinical evidence.

Central serous chorioretinopathy (CSCR) is part of the pachychoroid spectrum disorders, characterized by serous retinal detachments, retinal pigment epithelium alterations and dilation of choroidal vessels. No consensus exists regarding the clinical classification and the physiopathogenic mechanisms of the disease, delaying the comprehension of the most optimal treatment options. An overactivation of the mineralocorticoid receptor (MR) pathway in the choroid/retina has been suggested in CSCR. Since, MR antagonists could target the affected RPE/choroid in CSCR and have shown to act as disease modifier drugs inducing tissue remodeling in other organs (heart, kidney, vessels), we summarize here the pre-clinical and clinical evidence for using oral mineralocorticoid receptor antagonist in the treatment of CSCR.

Sostdc1 is expressed in all major compartments of developing and adult mammalian eyes.

PURPOSE: This study was conducted in order to study Sostdc1 expression in rat and human developing and adult eyes. METHODS: Using the yeast signal sequence trap screening method, we identified the Sostdc1 cDNA encoding a protein secreted by the adult rat retinal pigment epithelium. We determined by in situ hybridization, RT-PCR, immunohistochemistry, and western blot analysis Sostdc1 gene and protein expression in developing and postnatal rat ocular tissue sections. We also investigated Sostdc1 immunohistolocalization in developing and adult human ocular tissues. RESULTS: We demonstrated a prominent Sostdc1 gene expression in the developing rat central nervous system (CNS) and eyes at early developmental stages from E10.5 days postconception (dpc) to E13 dpc. Specific Sostdc1 immunostaining was also detected in most adult cells of rat ocular tissue sections. We also identified the rat ocular embryonic compartments characterized by a specific Sostdc1 immunohistostaining and specific Pax6, Sox2, Otx2, and Vsx2 immunohistostaining from embryonic stages E10.5 to E13 dpc. Furthermore, we determined the localization of SOSTDC1 immunoreactivity in ocular tissue sections of developing and adult human eyes. Indeed, we detected SOSTDC1 immunostaining in developing and adult human retinal pigment epithelium (RPE) and neural retina (NR) as well as in several developing and adult human ocular compartments, including the walls of choroidal and scleral vessels. Of utmost importance, we observed a strong SOSTDC1 expression in a pathological ocular specimen of type 2 Peters' anomaly complicated by retinal neovascularization as well in the walls ofother pathological extra-ocular vessels.  CONCLUSION: As rat Sostdc1 and human SOSTDC1 are dual antagonists of the Wnt/ß-catenin and BMP signaling pathways, these results underscore the potential crucial roles of these pathways and their antagonists, such as Sostdc1 and SOSTDC1, in developing and adult mammalian normal eyes as well as in syndromic and nonsyndromic congenital eye diseases.

INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT AT 2-MONTH INTERVALS REDUCES FOVEAL AVASCULAR ZONE ENLARGEMENT AND VISION LOSS IN RADIATION MACULOPATHY: A Pilot Study.

PURPOSE: To evaluate, in eyes with radiation maculopathy, the effect of 2-month-interval anti-vascular endothelial growth factor therapy on best-corrected visual acuity and foveal avascular zone (FAZ) enlargement using optical coherence tomography angiography. METHODS: Consecutive treatment-naive patients with radiation maculopathy after proton beam irradiation for choroidal melanoma were retrospectively included. Clinical and optical coherence tomography angiography data at baseline and the 6-month visit were recorded. Two independent observers measured FAZ area manually on 3 × 3-mm optical coherence tomography angiography images of the superficial capillary plexus and deep capillary plexus. Patients were encouraged to follow strictly a 2-month-interval intravitreal anti-vascular endothelial growth factor treatment by either bevacizumab or ranibizumab. Findings were analyzed based on the adherence to the treatment scheme. RESULTS: According to the adherence to the bimonthly anti-vascular endothelial growth factor treatment protocol, patients were categorized into 3 groups: treatment protocol (n = 19, strict adherence), variable intervals (n = 11, intervals other than 2 months), and no treatment (n = 11). The estimated radiation dose to the foveola in each group was 49 ± 16, 46 ± 17, and 46 ± 18 cobalt gray equivalent, respectively (P = 0.85). For the entire cohort, best-corrected visual acuity loss (P < 0.02) and FAZ enlargement (P < 0.0001) were observed over 6 months. Best-corrected visual acuity loss was significantly less pronounced in the treatment-protocol group than in the variable-interval and no-treatment groups (P = 0.007 and P = 0.004). The FAZ enlargement was lower in the treatment-protocol group compared with the variable-interval group for both superficial capillary plexus (P = 0.029) and deep capillary plexus (P = 0.03), and to the no-treatment group for the deep capillary plexus only (P = 0.016). CONCLUSION: Decrease in best-corrected visual acuity and FAZ enlargement on optical coherence tomography angiography occurred over 6 months in eyes with radiation maculopathy and were significantly reduced under 2-month-interval anti-vascular endothelial growth factor therapy.

PATTERNS OF CHORIOCAPILLARIS FLOW SIGNAL VOIDS IN CENTRAL SEROUS CHORIORETINOPATHY: An Optical Coherence Tomography Angiography Study.

PURPOSE: To investigate choriocapillaris flow signal void distribution on optical coherence tomography (OCT) angiography in central serous chorioretinopathy (CSCR) and its correlation to choroidal vessel morphology. METHODS: Fifty-three CSCR eyes (48 patients) and 34 healthy control eyes were included, retrospectively. Exclusion criteria were refractive error >2D, previous laser or photodynamic therapy, low-quality OCT angiography, or excessive shadowing artifacts. Choriocapillaris OCT angiography scans were processed by local-threshold binarization to identify signal voids, and extract their cumulative area. The locations of the two largest voids in each eye were reported on the corresponding enhanced depth imaging OCT raster scan. Choriocapillaris thickness and diameter of underlying outer choroidal vessels were measured at the level of flow voids and of adjacent outer choroidal vessels, not colocalizing with voids. RESULTS: There were 22 acute, 16 recurrent, and 15 chronic CSCR eyes. Total flow void area was larger in CSCR than control eyes. In univariate analysis, the total flow void area on OCT angiography increased with age (P = 0.0002), duration since CSCR diagnosis (P = 0.004), extension of autofluorescence alterations (P = 0.016), and CSCR severity (P < 0.0001). In multivariate analysis, age (P = 0.014) and CSCR type (P = 0.046) influenced independently the total flow void area. On enhanced depth imaging OCT, outer choroidal vessel diameter was higher (P < 0.0001), and choriocapillaris was thinner (P < 0.0001) at flow voids compared with adjacent sites, independently from eccentricity from the fovea. CONCLUSION: Choriocapillaris flow voids colocalize with choriocapillaris thinning and deep choroidal vessel dilation in CSCR eyes. Age and CSCR severity influence choriocapillaris flow, a key contributor to CSCR pathophysiology and clinical expression.

Primary rhegmatogenous retinal detachment: risk factors for macular involvement.

PURPOSE: Rhegmatogenous retinal detachment (RD) has diagnostically been divided into macula-OFF or macula-ON. The aim of this study was to describe the demographics and primary outcome of patients with RD following surgery with respect to the macular status, and to determine risk factors for macular involvement. METHODS: This prospective, observational, mono-centric cohort study was conducted at the Jules-Gonin Eye Hospital, from February 2015 until March 2017. The study included 194 eligible patients with primary RD. All patients underwent surgical treatment after baseline clinical examination. The dataset was analyzed using descriptive and analytic statistics. RESULTS: A total of 52.6% (102/194) of patients presented with macula-OFF RD. Mean age was 63.9 ± 12.0 vs. 59.7 ± 11.2 years in the OFF and ON group, respectively. There were 129 men (66.5%) and 65 (33.5%) women, and there were significantly more right eyes affected [right vs. left eyes 123 (63.4%) vs. 71 (36.6%), p = 0.000]. Significantly more myopes (<-3D) presented with a macula-ON RD (p = 0.04). There were more phakic patients in the cohort (55.7%), and phakic eyes were more likely to present with macula-ON RD (p = 0.01). Multivariate modeling showed that pseudophakic lens status and eyes with axial length less than 25 mm (p = 0.06) are independent predictive factors for macula-OFF RD (p = 0.02), whereas sex and laterality were not risk factors for macular involvement. CONCLUSION: Pseudophakic lens status and axial length < 25 mm are independent predictive factors for macula-OFF RD. While pseudophakic lens status is a recognized risk factor for RD, shorter axial length has not been previously identified as a risk factor for the macula-OFF RD.