Human TUBB3 mutations perturb microtubule dynamics, kinesin interactions, and axon guidance.

We report that eight heterozygous missense mutations in TUBB3, encoding the neuron-specific beta-tubulin isotype III, result in a spectrum of human nervous system disorders that we now call the TUBB3 syndromes. Each mutation causes the ocular motility disorder CFEOM3, whereas some also result in intellectual and behavioral impairments, facial paralysis, and/or later-onset axonal sensorimotor polyneuropathy. Neuroimaging reveals a spectrum of abnormalities including hypoplasia of oculomotor nerves and dysgenesis of the corpus callosum, anterior commissure, and corticospinal tracts. A knock-in disease mouse model reveals axon guidance defects without evidence of cortical cell migration abnormalities. We show that the disease-associated mutations can impair tubulin heterodimer formation in vitro, although folded mutant heterodimers can still polymerize into microtubules. Modeling each mutation in yeast tubulin demonstrates that all alter dynamic instability whereas a subset disrupts the interaction of microtubules with kinesin motors. These findings demonstrate that normal TUBB3 is required for axon guidance and maintenance in mammals.

Congenital isolated unilateral third nerve palsy in children: the diagnostic contribution of high-resolution MR imaging.

PURPOSE: To describe the neuroanatomical correlates of unilateral congenital isolated oculomotor palsy by means of high-resolution MRI. METHODS: Children with a clinical diagnosis of congenital isolated oculomotr palsy and with a high-resolution MRI acquisition targeted on the orbits and cranial nerves were selected and included in the study. An experienced pediatric neuroradiologist evaluated all the exams, assessing the integrity and morphology of extraocular muscles, oculomotor, trochlear and abducens nerves as well as optic nerves and globes. Clinical data and ophthalmologic evaluations were also collected. RESULTS: Six children (age range: 1-16 years; males: 3) were selected. All patients showed, on the affected side (left:right = 5:1), anomalies of the III nerve and extraocular muscles innervated by the pathological nerve. One patient had complete nerve agenesis, two patients showed a diffuse thinning of the nerve, from the brainstem to the orbit and 3 patients showed a distal thinning of the oculomotor nerve, starting at the level of the cavernous sinus. In all cases atrophy of corresponding muscles was noticed, but the involvement of the affected muscles varied with the nervous pattern of injury. CONCLUSIONS: High-resolution MRI represents a valuable tool for the diagnosis of III nerve anomalies in unilateral congenital IOP, showing different patterns of nerve involvement and muscular atrophy.

Paralog Studies Augment Gene Discovery: DDX and DHX Genes.

Members of a paralogous gene family in which variation in one gene is known to cause disease are eight times more likely to also be associated with human disease. Recent studies have elucidated DHX30 and DDX3X as genes for which pathogenic variant alleles are involved in neurodevelopmental disorders. We hypothesized that variants in paralogous genes encoding members of the DExD/H-box RNA helicase superfamily might also underlie developmental delay and/or intellectual disability (DD and/or ID) disease phenotypes. Here we describe 15 unrelated individuals who have DD and/or ID, central nervous system (CNS) dysfunction, vertebral anomalies, and dysmorphic features and were found to have probably damaging variants in DExD/H-box RNA helicase genes. In addition, these individuals exhibit a variety of other tissue and organ system involvement including ocular, outer ear, hearing, cardiac, and kidney tissues. Five individuals with homozygous (one), compound-heterozygous (two), or de novo (two) missense variants in DHX37 were identified by exome sequencing. We identified ten total individuals with missense variants in three other DDX/DHX paralogs: DHX16 (four individuals), DDX54 (three individuals), and DHX34 (three individuals). Most identified variants are rare, predicted to be damaging, and occur at conserved amino acid residues. Taken together, these 15 individuals implicate the DExD/H-box helicases in both dominantly and recessively inherited neurodevelopmental phenotypes and highlight the potential for more than one disease mechanism underlying these disorders.

Postnatal microcephaly and retinal involvement expand the phenotype of RPL10-related disorder.

Hemizygous missense variants in the RPL10 gene encoding a ribosomal unit are responsible for an X-linked syndrome presenting with intellectual disability (ID), autism spectrum disorder, epilepsy, dysmorphic features, and multiple congenital anomalies. Among 15 individuals with RPL10-related disorder reported so far, only one patient had retinitis pigmentosa and microcephaly was observed in approximately half of the cases. By exome sequencing, three Italian and one Spanish male children, from three independent families, were found to carry the same hemizygous novel missense variant p.(Arg32Leu) in RPL10, inherited by their unaffected mother in all cases. The variant, not reported in gnomAD, is located in the 28S rRNA binding region, affecting an evolutionary conserved residue and predicted to disrupt the salt-bridge between Arg32 and Asp28. In addition to features consistent with RPL10-related disorder, all four boys had retinal degeneration and postnatal microcephaly. Pathogenic variants in genes responsible for inherited retinal degenerations were ruled out in all the probands. A novel missense RPL10 variant was detected in four probands with a recurrent phenotype including ID, dysmorphic features, progressive postnatal microcephaly, and retinal anomalies. The presented individuals suggest that retinopathy and postnatal microcephaly are clinical clues of RPL10-related disorder, and at least the retinal defect might be more specific for the p.(Arg32Leu) RPL10 variant, suggesting a specific genotype/phenotype correlation.

A novel p.(Glu111Val) missense mutation in GUCA1A associated with cone-rod dystrophy leads to impaired calcium sensing and perturbed second messenger homeostasis in photoreceptors.

Guanylate Cyclase-Activating Protein 1 (GCAP1) regulates the enzymatic activity of the photoreceptor guanylate cyclases (GC), leading to inhibition or activation of the cyclic guanosine monophosphate (cGMP) synthesis depending on its Ca2+- or Mg2+-loaded state. By genetically screening a family of patients diagnosed with cone-rod dystrophy, we identified a novel missense mutation with autosomal dominant inheritance pattern (c.332A>T; p.(Glu111Val); E111V from now on) in the GUCA1A gene coding for GCAP1. We performed a thorough biochemical and biophysical investigation of wild type (WT) and E111V human GCAP1 by heterologous expression and purification of the recombinant proteins. The E111V substitution disrupts the coordination of the Ca2+ ion in the high-affinity site (EF-hand 3, EF3), thus significantly decreasing the ability of GCAP1 to sense Ca2+ (∼80-fold higher Kdapp compared to WT). Both WT and E111V GCAP1 form dimers independently on the presence of cations, but the E111V Mg2+-bound form is prone to severe aggregation over time. Molecular dynamics simulations suggest a significantly increased flexibility of both the EF3 and EF4 cation binding loops for the Ca2+-bound form of E111V GCAP1, in line with the decreased affinity for Ca2+. In contrast, a more rigid backbone conformation is observed in the Mg2+-bound state compared to the WT, which results in higher thermal stability. Functional assays confirm that E111V GCAP1 interacts with the target GC with a similar apparent affinity (EC50); however, the mutant shifts the GC inhibition out of the physiological [Ca2+] (IC50E111V ∼10 µM), thereby leading to the aberrant constitutive synthesis of cGMP under conditions of dark-adapted photoreceptors.

Expanding the Clinical and Genetic Spectrum of RAB28-Related Cone-Rod Dystrophy: Pathogenicity of Novel Variants in Italian Families.

The small Ras-related GTPase Rab-28 is highly expressed in photoreceptor cells, where it possibly participates in membrane trafficking. To date, six alterations in the RAB28 gene have been associated with autosomal recessive cone-rod dystrophies. Confirmed variants include splicing variants, missense and nonsense mutations. Here, we present a thorough phenotypical and genotypical characterization of five individuals belonging to four Italian families, constituting the largest cohort of RAB28 patients reported in literature to date. All probands displayed similar clinical phenotype consisting of photophobia, decreased visual acuity, central outer retinal thinning, and impaired color vision. By sequencing the four probands, we identified: a novel homozygous splicing variant; two novel nonsense variants in homozygosis; a novel missense variant in compound heterozygous state with a previously reported nonsense variant. Exhaustive molecular dynamics simulations of the missense variant p.(Thr26Asn) in both its active and inactive states revealed an allosteric structural mechanism that impairs the binding of Mg2+, thus decreasing the affinity for GTP. The impaired GTP-GDP exchange ultimately locks Rab-28 in a GDP-bound inactive state. The loss-of-function mutation p.(Thr26Asn) was present in a compound heterozygosis with the nonsense variant p.(Arg137*), which does not cause mRNA-mediated decay, but is rather likely degraded due to its incomplete folding. The frameshift p.(Thr26Valfs4*) and nonsense p.(Leu13*) and p.(Trp107*) variants, if translated, would lack several key structural components necessary for the correct functioning of the encoded protein.

Pathogenicity of new BEST1 variants identified in Italian patients with best vitelliform macular dystrophy assessed by computational structural biology.

BACKGROUND: Best vitelliform macular dystrophy (BVMD) is an autosomal dominant macular degeneration. The typical central yellowish yolk-like lesion usually appears in childhood and gradually worsens. Most cases are caused by variants in the BEST1 gene which encodes bestrophin-1, an integral membrane protein found primarily in the retinal pigment epithelium. METHODS: Here we describe the spectrum of BEST1 variants identified in a cohort of 57 Italian patients analyzed by Sanger sequencing. In 13 cases, the study also included segregation analysis in affected and unaffected relatives. We used molecular mechanics to calculate two quantitative parameters related to calcium-activated chloride channel (CaCC composed of 5 BEST1 subunits) stability and calcium-dependent activation and related them to the potential pathogenicity of individual missense variants detected in the probands. RESULTS: Thirty-six out of 57 probands (63% positivity) and 16 out of 18 relatives proved positive to genetic testing. Family study confirmed the variable penetrance and expressivity of the disease. Six of the 27 genetic variants discovered were novel: p.(Val9Gly), p.(Ser108Arg), p.(Asn179Asp), p.(Trp182Arg), p.(Glu292Gln) and p.(Asn296Lys). All BEST1 variants were assessed in silico for potential pathogenicity. Our computational structural biology approach based on 3D model structure of the CaCC showed that individual amino acid replacements may affect channel shape, stability, activation, gating, selectivity and throughput, and possibly also other features, depending on where the individual mutated amino acid residues are located in the tertiary structure of BEST1. Statistically significant correlations between mean logMAR best-corrected visual acuity (BCVA), age and modulus of computed BEST1 dimerization energies, which reflect variations in the in CaCC stability due to amino acid changes, permitted us to assess the pathogenicity of individual BEST1 variants. CONCLUSIONS: Using this computational approach, we designed a method for estimating BCVA progression in patients with BEST1 variants.

Multimodal Imaging in Autosomal Dominant Cone-Rod Dystrophy Caused by Novel CRX Variant.

AIM: To characterize by multimodal approach the phenotype of patients from a 3 generations pedigree, affected by autosomal dominant cone-rod dystrophy (CRD), found to carry a novel pathogenic variant in the cone-rod homeobox-containing (CRX) gene. METHODS: Examination of the adult patients included the following tests: visual acuity, multicolour imaging, spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF) and OCT angiography (OCT-A) recordings. In a 2.5-year-old child, cycloplegic refraction, fundoscopy, ocular motility evaluation and electrophysiological exams were performed. Next Generation Sequencing of patients' DNA has been carried out. RESULTS: A novel CRX pathogenic variant has been identified in our patients. The 2.5-year-old child in the third generation was found to have inherited the variant, with no clinical signs of the condition, but electroretinographic abnormalities in the scotopic component. In the adult patients, diffuse atrophy of the retinal pigment epithelium/photoreceptor complex in the macular region was evident at the OCT and FAF, while OCT-A showed choriocapillaris density reduction. CONCLUSIONS: Multimodal study allowed the characterization of a peculiar form of CRD. The novel pathogenic variant seems to have a different effect on the phenotype if compared with a previously described similar one, giving an insight into the pathogenic mechanism of CRX-related retinal dystrophies and offering valuable information that could lead to the development of possible future therapies.

Developmental visual deprivation: long term effects on human cone driven retinal function.

PURPOSE: To assess whether infantile visual deprivation induced by developmental cataract may influence the cone-driven retinal function in humans. METHODS: A total of 14 patients with history of bilateral developmental cataract (DC), who had undergone uncomplicated cataract extraction surgery and intraocular lens implant, and 14 healthy subjects (HS) were enrolled. All patients underwent complete ophthalmological and orthoptic evaluations and best-corrected visual acuity measurement. Light-adapted full-field electroretinograms (ERG) and photopic negative responses (PhNR) were recorded to obtain a reliable measurement of the outer/inner retinal function and of the retinal ganglion cells' function, respectively. RESULT: Mean values of light-adapted ERG a- and b-wave implicit times were slightly delayed when compared to HS values. Light-adapted ERG a-wave amplitude mean values showed borderline values (p = 0.001), whereas a-wave amplitude analysis at 5 ms, b-wave and PhNR amplitude mean values showed no significant differences when compared to control values. No significant correlations were found when age at surgery, time elapsed from surgery, duration of the visual deprivation, age at examination, age at first detection of the opacity, BCVA and electrophysiological parameters were plotted together. Coherently with morphological studies, the extremely light bioelectrical impairment of the cone pathway in our cohort of patients describes minimal functional abnormalities of a well-structured retina that is not completely mature. CONCLUSIONS: Our present results, combined to those of our previous work on congenital cataracts, allow us to enhance the comprehension of functional developmental mechanisms of children's retinas and highlight the relevance of the timely treatment of lens opacities during infancy.

Pediatric keratoconus and iontophoretic corneal crosslinking: refractive and topographic evidence in patients underwent general and topical anesthesia, 18 months of follow-up.

To evaluate the efficiency and safety of iontophoretic transepithelial corneal crosslinking in pediatric patients with progressive keratoconus underwent general or topical anesthesia in 18 months follow-up. 13 patients (13 eyes) diagnosed with progressive keratoconus underwent corneal CXL with iontophoresis (I-CXL). Riboflavin solution was administered by iontophoresis for 5 min, and then UV-A irradiation (10 mW/cm) was performed for 9 min. Preoperative and post-operative visits at 1, 6, 12, and 18 months assessed the following parameters: uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), slit-lamp biomicroscopy, corneal topography, optical tomography, and pachymetry with Pentacam (Oculus Optikgeräte GmbH, Wetzlar, Germany), endothelial biomicroscopy (Konan Specular Microscope; Konan Medical, Inc., Hyogo, Japan). The paired Student t test was used to compare data during the follow-up. 10 males and 3 females with a mean age of 15.4 ± 1.7 years (range 11-18 years) were included. The results showed a stabilization of the refractive UCVA and BCVA as early as the first post-operative month, with a slight improvement over time. The Kmax remained stable throughout follow-up (p = 0.04). Transepithelial collagen crosslinking by iontophoresis, unlike other transepithelial techniques seems to halt pediatric keratoconus progression over 18 months. This is the second study evaluating CXL with iontophoresis in pediatric patients with progressive keratoconus with 18 months of follow-up using two different ways of anesthesia.

Refractive surgery for accommodative esotropia: 5-year follow-up.

PURPOSE: To assess the long-term effectiveness and safety of refractive surgery with LASIK or photorefractive keratectomy (PRK) for treating accommodative esotropia in adults. METHODS: All patients with accommodative esotropia treated with LASIK or PRK until December 2007 and with a minimum follow-up of 5 years were retrospectively included. RESULTS: LASIK was performed on 44 eyes of 22 patients (12 women, 10 men; mean age: 22.7 ± 2.9 years). Mean postoperative follow-up was 62.1 ± 3.2 months. PRK was performed on 16 eyes of 8 patients (4 women, 4 men; mean age: 23.7 ± 1.7 years). Mean postoperative follow-up was 61.3 ± 2.8 months. At the 5-year follow-up, the mean cycloplegic refraction was more hyperopic in the PRK group (0.3 ± 0.8 vs 0.06 ± 0.3 diopters, P = .01). Correction of esotropia to esophoria or orthotropia was present in 21 patients (95.4%) treated with LASIK and in all patients treated with PRK. CONCLUSIONS: Both LASIK and PRK were effective in the long-term reduction of accommodative esotropia.

Short-term effects of vision trainer rehabilitation in patients affected by anisometropic amblyopia: electrofunctional evaluation.

PURPOSE: The aim of the present study was to evaluate the short-term effects of the vision trainer rehabilitation technique on retinal and post-retinal function in young amblyopic patients outside the critical visual developmental period. METHODS: Twenty-one patients (mean age 12.2 ± 2.7 years, ranging from 9.1 to 18 years) affected by unilateral anisometropic amblyopia were studied, providing 21 amblyopic eyes (AE) and 21 sound eyes (SE). Thirty eyes from 15 age-similar normal subjects served as controls. All subjects underwent extensive ophthalmologic characterization to exclude any disease not related to amblyopia. All AE were subjected to rehabilitation sessions performed by the Retimax vision trainer (VT) program. The protocol consisted of 2 sessions per week, each lasting 10 min, for 10 consecutive weeks. Before and after the rehabilitation, electrophysiological [pattern electroretinogram (PERG) and visual evoked potential (VEP)] and psychophysical [best corrected visual acuity (BCVA) and microperimetry] data were collected from AE and SE. RESULTS: When comparing baseline data with those collected at the end of the study, PERG P50-N95 amplitude and BCVA values from AE had improved significantly by the end of the study (p < 0.05). Our electrophysiological findings also showed some abnormalities in SE when the data were compared to control eyes. We found a significant correlation (p < 0.05) between PERG amplitude and VEP implicit time in SE after visual rehabilitation. CONCLUSIONS: Short-term visual rehabilitation performed by the VT program ameliorated the electrofunctional and psychophysical parameters of vision in children outside the critical developmental period, thus indicating that VT might be a potential adjuvant therapy of traditional patching treatment.

Essential infantile esotropia: postoperative motor outcomes and inferential analysis of strabismus surgery.

BACKGROUND: The aim of this retrospective study is a long-term evaluation of postoperative motor outcomes and the inferential analysis of strabismus surgery in infant eyes with essential infantile esotropia. METHODS: 576 patients were compatible with the criteria: confirmed EIE diagnosis, angle ≥ 30 pD, absence of associated ocular anomalies, onset by 6 months of age, absence of hyperopia > 3 Diopters, operation before age 4. Preoperative deviation classes (30-40 pD, 41-59 pD, ≥ 60 pD) were established, different types of surgery were performed. Follow-up was conducted for 5 years after surgery. Longitudinal data were analyzed using general linear mixed models stratified according to the class of pre-operative deviation. A random intercept and a random slope with time (in months) was assumed with an unstructured within subject correlation structure for repeated measurements. RESULTS: In patients with preoperative angle ≤ 40 pD, a significant interaction effect for intervention by time (F5,155.9 = 3.56, p = 0.004) and a significant intervention effect (F5,226.1 = 6.41, p < 0.001) on residual deviation were observed; only the intervention 5 showed a residual deviation inside the limits of a partial success. In Class 41-59, a significant interaction effect for intervention by time (F4,166.7 = 5.16, p = 0.001), intervention (F4,178.1 = 2.48, p = 0.046) and time (F1,174.6 = 9.99, p = 0.002) on residual deviation were observed; intervention 7 had the highest degree of stability showing an outcome within the range of a partial success. In Class ≥ 60 pD no significant effect for intervention (F4,213.9 = 0.74, p = 0.567), time (F1,169.5 = 0.33, p = 0.569) or intervention by time (F4,160.9 = 1.08, p = 0.368) on residual deviation was observed; intervention 3,6 and 7 resulted in a residual deviation within the range of a partial success. CONCLUSIONS: We suggest, where possible, a two-horizontal muscles approach in small angle EIE, while a multiple muscles surgery in large angle EIE.

Long-term outcome of primary versus secondary intraocular lens implantation after simultaneous removal of bilateral congenital cataract.

BACKGROUND: Long-term outcomes of intraocular lens (IOL) implantation for congenital cataract in children under 2 years old are still undetermined. METHODS: We retrospectively reviewed all cases of bilateral congenital cataract who had undergone simultaneous bilateral cataract removal with posterior capsulotomy and central anterior vitrectomy between 1990 and 2010. Patients randomly underwent primary IOL implantation or secondary IOL implantation after a period of contact lens wear. The two groups were compared for visual outcome and complications during follow-up. RESULTS: Cataract removal and primary IOL implantation was performed in 30 eyes (15 patients; nine males, six females) at a mean age of 6.8 ± 4.2 months. After 79.31 ± 63.4 months, best-corrected visual acuity (BCVA) was 0.53 ± 0.36 EDTRS LogMAR. In 36 eyes (18 patients, 11 males, seven females) the lens was removed at a mean age of 5.42 ± 2.80 months, and after 32.0 ± 6.1 months of contact lens utilization, secondary IOL implantation was performed. After 109.0 ± 33.8 months, BCVA was 0.54 ± 0.4 ETDRS LogMAR. The association between age at surgery and final visual acuity and the difference between the two groups concerning type of cataract at baseline, BCVA and refractive error at last visit, incidence of posterior capsular opacification, glaucoma, strabismus, and nystagmus during follow-up were not significant (p > 0.05). Myopic shift was more frequent in eyes undergone primary IOL implantation (p < 0.001). CONCLUSIONS: Similar visual outcome and complications were observed during long-term follow-up after both primary and secondary IOL implantation following simultaneous bilateral congenital cataract removal with posterior capsulotomy and central anterior vitrectomy.

Adalimumab for juvenile idiopathic arthritis-associated uveitis.

PURPOSE: To assess the long-term outcomes and complications of patients with uveitis from juvenile idiopathic arthritis (JIA) treated with adalimumab. METHODS: Prospective interventional case series. All patients who underwent treatment with adalimumab for JIA and anterior uveitis were prospectively included in the study. The anterior chamber inflammation was evaluated according to the Standardization of Uveitis Nomenclature criteria. RESULTS: Twenty-one patients (16 females, five males, 38 eyes) were included in the study. Mean age of patients at referral was 11.1 ± 3.8 (5-17) years. Before initiation of treatment, mean duration of arthritis was 7.0 ± 5.5 (median, 6) months, mean duration of uveitis was 7.0 ± 4.4 (median, 7) months. Oligoarticular arthritis was present in 15 cases (71 %), polyarticular arthritis in six cases (28 %). After a mean follow-up of 18.2 ± 7.7 (9-41) months, resolution of anterior chamber inflammation was obtained in 29/38 eyes (76 %). The anterior uveitis flare rate during the 12 months prior to enrollment was 1.6 ± 0.4/year, and was reduced during adalimumab treatment to 0.7 ± 0.3/year (p<0.001). A significant decrease of the number of relapses/month was present after onset of treatment with adalimumab (0.18 ± 0.2 before versus 0.02 ± 0.1 after treatment onset, p<0.001). No significant correlation was found between relapse number and age, sex, type of JIA and doses of previous steroid treatment (p>0.05). CONCLUSION: Adalimumab showed to be effective and relatively safe for treatment of JIA-associated uveitis.

Heterozygous mutations of the kinesin KIF21A in congenital fibrosis of the extraocular muscles type 1 (CFEOM1).

Congenital fibrosis of the extraocular muscles type 1 (CFEOM1; OMIM #135700) is an autosomal dominant strabismus disorder associated with defects of the oculomotor nerve. We show that individuals with CFEOM1 harbor heterozygous missense mutations in a kinesin motor protein encoded by KIF21A. We identified six different mutations in 44 of 45 probands. The primary mutational hotspots are in the stalk domain, highlighting an important new role for KIF21A and its stalk in the formation of the oculomotor axis.

Morphovascular changes after anti-VEGF intravitreal injection for a choroidal neovascularization secondary to COVID-19 infection in a pediatric patient.

Choroidal neovascularization (CNV) is a common pathologic lesion that occurs in various chorioretinopathy. Although the incidence of CNV is quite rare in children and adolescents, these lesions have a severe impact on visual acuity and quality of life over patients' lifetime. The management of CNV in pediatric patients is challenging, clear guidelines are limited due to a lack of randomized clinical trials. However, the more promising option is the use of vascular endothelial growth factor (VEGF) inhibitors. We reported a case of recurrent idiopathic choroidal neovascularization in a healthy pediatric patient after COVID 19 infection. Optical coherence tomography angiofraphy (OCTA) showed, in a non invasive way, a choroidal neovascularization at the posterior pole including macula and superior temporal arcade in the right eye, while the left eye was unaffected. In order to inactivate the neovascularization, intravitreal injections of anti-VEGF (Lucentis-Ranibizumab 0.3 mL) were performed in the right eye. Six months after the injections BCVA of the right eye was improved from 0.7 logMAR to 0.2 logMAR. OCT-A examination did not detect any signs of attivation of the preexistent neovascularization. It is reasonable to assert that Anti-VEGF could be the main treatment in case of choroidal neovascularization in young patients after COVID 19 infection due to the high chorioretinal level of VEGF-A described in these diseases.

Long-term effects of early/late-onset visual deprivation on macular and retinal nerve fibers layer structure: A pilot study.

BACKGROUND/AIMS: Tomographic analysis of macular and peripapillary retinal nerve fibers layer (RNFL) thickness in patients with history of congenital (CC) and developmental cataract (DC). METHODS: Analysis of macular and RNFL thickness using a spectral-domain optical coherence tomography was performed. Retinal layers thickness was measured using the internal segmentation software. Measurements of affected (unilateral and bilateral), contralateral eyes and control eyes were compared. RESULTS: Patients with history of CC or DC (n = 13 and 11 respectively) and 35 healthy control subjects were enrolled. Thicker inner and outer nuclear layers (INL, ONL) and thicker ONL were found when CC and DC group when compared to controls respectively. Bilateral CC showed the most relevant differences. Slight thickening of CC inner retinal layers were found when compared to DC. Increased superonasal RNFL thickness was found in CC group when compared to DC and controls. Thickening of RNFL of contralateral unaffected eyes of unilateral CC were found when compared to controls. CONCLUSION: Significant macular and RNFL thickness changes between CC, DC patients and controls that partially involve also contralateral unaffected eyes of unilateral congenital cataract were found. CC and DC groups show significant differences only in inner retinal layers thickness. Our data suggest that early visual deprivation may influence retinal arrangements occurring during development involving predominantly the outer nuclear layer and para/perifoveal inner retinal layers, and confirm that early treatment of CC allow to achieve better long-term visual outcome. Moreover functional and structural data support the hypothesis that unilateral amblyopia is not exclusively an unilateral issue.

Bilateral methicillin-resistant Staphylococcus aureus keratitis following hyperopic photorefractive surgery.

To report clinical manifestations of a female patient with bilateral bacterial keratitis following photorefractive keratectomy (PRK). Bilateral PRK was performed for moderate hyperopia. Bandage contact lenses were fitted at the conclusion of the surgery. Bilateral infectious keratitis with hypopion was diagnosed within 4 days after surgery. Smear and culture were obtained and showed the presence of methicillin-resistant Staphylococcus aureus (MRSA). The patient was treated with systemic prednisone and topical antibiotics (vancomycin, tobramycin and netylmicin) and betamethasone. After 1 month corneal leukoma was still present and remained unchanged during the following 7 months. Infectious keratitis is a rare complication of PRK that appears early in the postoperative period. MRSA keratitis may determine long-term visual impairment despite prompt therapeutic intervention.

A case of retinal vascular involvement in a 6-year-old patient with Covid-19.

PURPOSE: This study evaluated fundus changes in a 6-year-old child who contracted Sars-CoV-2 without developing symptoms of the disease. MATERIALS AND METHODS: The patient underwent a complete ophthalmic evaluation, which included assessment of visual acuity with and without correction, extensive ophthalmological examination, cicloplegic refraction by retinoscopy and funduscopic examination, OCT, and angio-OCT examination. RESULTS: Fundoscopic examination in a young patient with previous Sars-CoV-2 infection showed marked vascular tortuosity, evident both at the posterior pole and retinal periphery, especially on the arterial vasculature, and cotton wool spots along the retinal vessels, highlightable also at OCT and angio-OCT examination. These alterations persist at a 6-month follow-up. CONCLUSIONS: In COVID-19 infection, even in asymptomatic pediatric patients, vasculitis develops also affecting the retinal vessels, appreciable on fundus examination. A thorough eye examination in all COVID-19 patients with close follow-up is therefore important. This is the first case report on retinal changes in a pediatric patient.