Comparison Between Monofocal and Aspheric Monofocal Intraocular Lens With Higher Order Aspheric Optic in Pediatric Patients: Early Outcomes.

PURPOSE: To retrospectively compare the visual acuity outcomes for far, intermediate, and near vision of an aspheric monofocal intraocular lens (IOL) with higher order aspheric optic with a monofocal IOL in pediatric patients. METHODS: Thirty-eight eyes of 38 patients (mean age: 9.0 ± 2.3 years) affected by monolateral infantile cataract were evaluated 6 months after surgery performed with simultaneous IOL implantation. The Tecnis Eyhance ICB00 aspheric monofocal IOL (Johnson & Johnson Vision) was implanted in 17 eyes (Tecnis Eyhance group, mean age: 8.9 ± 2.5 years) and the Tecnis PCB00 monofocal IOL (Johnson & Johnson Vision) was implanted in 21 eyes (control group, mean age: 9.1 ± 2.2 years). Corrected visual acuity expressed in logarithm of the minimum angle of resolution (logMAR) was assessed for distance (CDVA) and, expressed in Jaeger standard, for intermediate (DCIVA) and near vision (CNVA). DCIVA was measured with distance correction and without addition. The Mann-Whitney test for two independent samples was performed, and a P value less than .05 was considered statistically significant. RESULTS: Six months postoperatively, mean CDVA was 0.20 ± 0.2 logMAR and mean DCIVA and CNVA were 5 ± 1 and 2 ± 1 Jaeger, respectively, in the Tecnis Eyhance group. In the control group, mean CDVA was 0.21 ± 0.2 logMAR and mean DCIVA and CNVA were 8 ± 1 and 3 ± 1 Jaeger, respectively. Only DCIVA showed a significant statistical difference between groups (P < .0001). CONCLUSIONS: In pediatric patients, the aspheric monofocal IOL with higher order aspheric optic seems to provide better intermediate distance visual acuity than a monofocal one, whereas no significant difference was observed for CDVA and CNVA. [J Refract Surg. 2024;40(10):e724-e727.].

Effectiveness of Defocus Incorporated Multiple Segments in Slowing Myopia Progression in Pediatric Patients as a Function of Age: Three-Year Follow-Up.

Background: The purpose of this study is to evaluate the effectiveness of Defocus Incorporated Multiple Segments (DIMSs) in slowing myopia progression in pediatric patients as a function of age. Methods: This was a non-randomized experimenter-masked retrospective controlled observational study of European individuals aged 6-16 years with progressive myopia but no ocular pathology. We retrospectively reviewed the charts of the participants allocated to receive DIMS spectacles (Hoya® MiyoSmart®) or single-vision spectacle lenses (control group). Cycloplegic spherical equivalent (SE) and axial length (AL) were measured at baseline and at 12-, 24-, and 36-month follow-ups. The results were stratified by age into four groups: patients wearing DIMS spectacles older or younger than 10 years of age (group A, 20 patients mean age 13.6 ± 2.2, and group C, 20 patients mean age 9.0 ± 1.2) and age-matched control groups (group B, 18 patients mean age 13.2 ± 2.5, and group D, 22 patients mean age 8.5 ± 0.9). Results: At 36 months, SE and AL increase were significantly reduced in groups A and C, respectively, compared to groups B and D (p < 0.05). Linear regression analysis showed a significant correlation (p < 0.05) between patient age and myopia progression for SE in groups A and C, but only in group A for AL. Groups B and D did not show any significant correlation (p > 0.05). Conclusions: DIMS spectacles seem to slow myopia progression in pediatric patients; however, their effectiveness shows the greatest results in children older than 10 years of age. Moreover, our findings suggest that AL may be the more reliable parameter for evaluating myopia progression.

Genotypic and Phenotypic Characterization of a Cohort of Patients Affected by Rod Cyclic Nucleotide Channel-Associated Retinitis Pigmentosa.

INTRODUCTION: Retinitis pigmentosa (RP), a heterogeneous inherited retinal disorder causing gradual vision loss, affects over 1 million people worldwide. Pathogenic variants in CNGA1 and CNGB1 genes, respectively, accounting for 1% and 4% of cases, impact the cyclic nucleotide-gated channel in rod photoreceptor cells. The aim of this study was to describe and compare genotypic and clinical characteristics of a cohort of patients with CNGA1- or CNGB1-related RP and to explore potential genotype-phenotype correlations. METHODS: The following data from patients with CNGA1- or CNGB1-related RP, followed in five Italian inherited retinal degenerations services, were retrospectively collected: genetic variants in CNGA1 and CNGB1, best-corrected visual acuity (BCVA), ellipsoid zone (EZ) width, fundus photographs, and short-wavelength fundus autofluorescence (SW-AF) images. Comparisons and correlation analyses were performed by first dividing the cohort in two groups according to the gene responsible for the disease (CNGA1 and CNGB1 groups). In parallel, the whole cohort of RP patients was divided into two other groups, according to the expected impact of the variants at protein level (low and high group). RESULTS: In total, 29 patients were recruited, 11 with CNGA1- and 18 with CNGB1-related RP. In both CNGA1 and CNGB1, 5 novel variants in CNGA1 and 5 in CNGB1 were found. BCVA was comparable between CNGA1 and CNGB1 groups, as well as between low and high groups. CNGA1 group had a larger mean EZ width compared to CNGB1 group, albeit not statistically significant, while EZ width did not differ between low and high groups A statistically significant correlation between EZ width and BCVA as well as between EZ width and age were observed in the whole cohort of RP patients. Fundus photographs of all patients in the cohort showed classic RP pattern, and in SW-AF images an hyperautofluorescent ring was observed in 14/21 patients. CONCLUSION: Rod CNG channel-associated RP was demonstrated to be a slowly progressive disease in both CNGA1- and CNGB1-related forms, making it an ideal candidate for gene augmentation therapies.

Voretigene neparvovec for inherited retinal dystrophy due to RPE65 mutations: a scoping review of eligibility and treatment challenges from clinical trials to real practice.

Biallelic mutations in the RPE65 gene affect nearly 8% of Leber Congenital Amaurosis and 2% of Retinitis Pigmentosa cases. Voretigene neparvovec (VN) is the first gene therapy approach approved for their treatment. To date, real life experience has demonstrated functional improvements following VN treatment, which are consistent with the clinical trials outcomes. However, there is currently no consensus on the characteristics for eligibility for VN treatment. We reviewed relevant literature to explore whether recommendations on patient eligibility can be extrapolated following VN marketing. We screened 166 papers through six research questions, following scoping reviews methodology, to investigate: (1) the clinical and genetic features considered in VN treatment eligibility; (2) the psychophysical tests and imaging modalities used in the pre-treatment and follow-up; (3) the potential correlations between visual function and retinal structure that can be used to define treatment impact on disease progression; (4) retinal degeneration; (5) the most advanced testing modalities; and (6) the impact of surgical procedure on treatment outcomes. Current gaps concerning patients' eligibility in clinical settings, such as pre-treatment characteristics and outcomes are not consistently reported across the studies. No upper limit of retinal degeneration can be defined as the univocal factor in patient eligibility, although evidence suggested that the potential for function rescue is related to the preservation of photoreceptors before treatment. In general, paediatric patients retain more viable cells, present a less severe disease stage and show the highest potential for improvements, making them the most suitable candidates for treatment.

A multidisciplinary approach to inherited retinal dystrophies from diagnosis to initial care: a narrative review with inputs from clinical practice.

BACKGROUND: Non-syndromic inherited retinal dystrophies (IRDs) such as retinitis pigmentosa or Leber congenital amaurosis generally manifest between early childhood and late adolescence, imposing profound long-term impacts as a result of vision impairment or blindness. IRDs are highly heterogeneous, with often overlapping symptoms among different IRDs, and achieving a definite diagnosis is challenging. This narrative review provides a clinical overview of the non-syndromic generalized photoreceptor dystrophies, particularly retinitis pigmentosa and Leber congenital amaurosis. The clinical investigations and genetic testing needed to establish a diagnosis are outlined, and current management approaches are discussed, focusing on the importance of the involvement of an interdisciplinary team from diagnosis and initial care to long-term follow-up and support. RESULTS: The effective management of IRDs requires a multidisciplinary, and ideally interdisciplinary, team of experts knowledgeable about IRDs, with experienced professionals from fields as diverse as ophthalmology, neuropsychiatry, psychology, neurology, genetics, orthoptics, developmental therapy, typhlology, occupational therapy, otolaryngology, and orientation and mobility specialties. Accurate clinical diagnosis encompasses a range of objective and subjective assessments as a prerequisite for the genetic testing essential in establishing an accurate diagnosis necessary for the effective management of IRDs, particularly in the era of gene therapies. Improvements in genome sequencing techniques, such as next-generation sequencing, have greatly facilitated the complex process of determining IRD-causing gene variants and establishing a molecular diagnosis. Genetic counseling is essential to help the individual and their family understand the condition, the potential risk for offspring, and the implications of a diagnosis on visual prognosis and treatment options. Psychological support for patients and caregivers is important at all stages of diagnosis, care, and rehabilitation and is an essential part of the multidisciplinary approach to managing IRDs. Effective communication throughout is essential, and the patient and caregivers' needs and expectations must be acknowledged and discussed. CONCLUSION: As IRDs can present at an early age, clinicians need to be aware of the clinical signs suggesting visual impairment and follow up with multidisciplinary support for timely diagnoses to facilitate appropriate therapeutic or rehabilitation intervention to minimize vision loss.

Congenital heart defects in CTNNB1 syndrome: Raising clinical awareness.

CTNNB1 [OMIM *116806] encodes ß-catenin, an integral part of the cadherin/catenin complex, which functions as effector of Wnt signaling. CTNNB1 is highly expressed in brain as well as in other tissues, including heart. Heterozygous CTNNB1 pathogenic variations are associated with a neurodevelopmental disorder characterized by spastic diplegia and visual defects (NEDSDV) [OMIM #615075], featuring psychomotor delay, intellectual disability, behavioral disturbances, movement disorders, visual defects and subtle facial and somatic features. We report on a new series of 19 NEDSDV patients (mean age 10.3 years), nine of whom bearing novel CTNNB1 variants. Notably, five patients showed congenital heart anomalies including absent pulmonary valve with intact ventricular septum, atrioventricular canal with hypoplastic aortic arch, tetralogy of Fallot, and mitral valve prolapse. We focused on the cardiac phenotype characterizing such cases and reviewed the congenital heart defects in previously reported NEDSDV patients. While congenital heart defects had occasionally been reported so far, the present findings configure a higher rate of cardiac anomalies, suggesting dedicated heart examination to NEDSDV clinical management.

Simultaneous transepithelial topographic-guided laser and cross-linking to correct irregular astigmatism in a pediatric patient.

PURPOSE: To evaluate an original approach for treating corneal ectasia and irregular astigmatism secondary to penetrating trauma in a pediatric patient. CASE REPORT: An 11 year old patient had a penetrating trauma in right eye when he was two and the refractive error was +1.50 diopters sphere -6.00 diopters cylinder axis 95°. To correct irregular astigmatism, the patient underwent simultaneous transepithelial topographic-guided laser Central Corneal Remodeling (CCR) and Corneal Cross-linking (CXL) in the attempt to regularize corneal ectasia and to improve the quality of vision. Uncorrected and Corrected Distance Visual Acuity were measured using Efficacy and Safety indexes; objective and subjective qualities of vision were evaluated using respectively corneal morphological irregularity index and National Eye Institute Visual Function questionnaires. CONCLUSIONS: Twelve month follow up suggests that simultaneous CCR and CXL could be effective to improve the quality of vision and to halt the progression of post-traumatic ectasia in pediatric patients.

Superficial and Deep Capillary Plexuses: Potential Biomarkers of Focal Retinal Defects in Eyes Affected by Macular Idiopatic Epiretinal Membranes? A Pilot Study.

Inner macular layers are the most involved in the retinal distortion caused by idiopathic epiretinal membrane (iERM). They represent the anatomical structures in which the superficial (SCP) and deep (DCP) capillary plexus are embedded. We quantified flow signal (FS) in these capillary plexuses using Swept Source OCT angiography to identify possible markers for postoperative outcome. The software ImageJ was used to quantify the FS in a 150 µm radius area around each point analyzed by MAIA microperimeter. In 16 patients with unilateral iERM, focal light sensitivity (FLS) in the para- and perimacular areas was measured to evaluate macular function in 24 points overlapping macular plexuses and compared with normal fellow eyes (FEs). t-Test for independent samples iERM eyes (iERMEs) vs. fellow eyes (FEs) and Pearson correlation coefficient of FS vs. FLS in each point were calculated. A level of p < 0.05 was accepted as statistically significant. As a whole, FLS was significantly higher in FEs vs. ERMEs (p < 0.001); FS in both SCP and DCP was not significantly different between ERMEs and FEs (p = 0.827, p = 0.791). Correlation in focal retinal areas between FLS and FS in ERMEs was significant in SCP (p = 0.002) and not significant in DCP (p = 0.205); in FEs was significant in both SCP (p < 0.001) and DCP (p = 0.022). As previously described, these defective areas were located mainly in sites of distortion of retinal layers; therefore, it can be hypothesized that a focal change in FS, occurring mostly in SCP, could be involved in the onset of the functional defect.

A Novel Autosomal Recessive Variant of the NRL Gene Causing Enhanced S-Cone Syndrome: A Morpho-Functional Analysis of Two Unrelated Pediatric Patients.

Enhanced S-cone syndrome (ESCS) is a rare autosomal recessive retinal degeneration mainly associated with pathogenic variations in the NR2E3 gene. Only a few pathogenic variations in the NRL gene associated with ESCS have been reported to date. Here, we describe the clinical and genetic findings of two unrelated pediatric patients with a novel frameshift homozygous variant in the NRL gene. Fundus examinations showed signs of peripheral degeneration in both patients, more severe in Proband 2, with relative sparing of the macular area. Spectral domain optical coherence tomography (SD-OCT) revealed a significant macular involvement with cysts in Proband 1, and minimal foveal alteration with peripheral retina involvement in Proband 2. Visual acuity was abnormal in both patients, but more severely affected in Proband 1 than Proband 2. The electroretinogram recordings showed reduced scotopic, mixed and single flash cone responses, with a typical supernormal S-cone response, meeting the criteria for a clinical diagnosis of ESCS in both patients. The present report expands the clinical and genetic spectrum of NRL-associated ESCS, and confirms the age-independent variability of phenotypic presentation already described in the NR2E3-associated ESCS.

Narrative medicine to investigate the quality of life and emotional impact of inherited retinal disorders through the perspectives of patients, caregivers and clinicians: an Italian multicentre project.

OBJECTIVES: Although inherited retinal disorders (IRDs) related to the gene encoding the retinal pigment epithelium 65kD protein (RPE65) significantly impact the vision-related quality of life (VRQoL), their emotional and social aspects remain poorly investigated in Italy. Narrative Medicine (NM) reveals the more intimate aspects of the illness experience, providing insights into clinical practice. DESIGN AND SETTING: This NM project was conducted in Italy between July and December 2020 and involved five eye clinics specialised in IRDs. Illness plots and parallel charts, together with a sociodemographic survey, were collected through the project's website; remote in-depth interviews were also conducted. Narratives and interviews were analysed through NVivo software and interpretive coding. PARTICIPANTS: 3 paediatric and 5 adult patients and eight caregivers participated in the project; 11 retinologists globally wrote 27 parallel charts; 5 professionals from hospital-based multidisciplinary teams and one patient association member were interviewed. RESULTS: Findings confirmed that RPE65-related IRDs impact VRQoL in terms of activities and mobility limitations. The emotional aspects emerged as crucial in the clinical encounter and as informative on IRD management challenges and real-life experiences, while psychological support was addressed as critical from clinical diagnosis throughout the care pathway for both patients and caregivers; the need for an IRDs 'culture' emerged to acknowledge these conditions, and therefore, promoting diversity within society. CONCLUSIONS: The project was the first effort to investigate the impact of RPE65-related IRDs on the illness experience through NM, concomitantly addressing the perspectives of paediatric and adult patients, caregivers and healthcare professionals and provided preliminary insights for the knowledge of RPE65-related IRDs and the clinical practice.

Genetics of Inherited Retinal Diseases in Understudied Ethnic Groups in Italian Hospitals.

Purpose: Describing the clinical and genetic features of an ethnically heterogeneous group of (inherited retinal diseases) IRD patients from different underrepresented countries, referring to specialized Italian Hospitals, and expanding the epidemiological spectrum of the IRD in understudied populations. Methods: The patients' phenotypes underwent were characterized by exhaustive ophthalmological examinations, including morpho-functional testing. Genetic testing was performed using next-generation sequencing (NGS) and gene sequencing panels targeting a specific set of genes, Sanger sequencing and-when necessary-multiplex ligation-dependent probe amplification (MLPA) to better identify the genotype. When possible, segregation analysis was performed in order to confirm unsolved cases. Results: The article reports the results of the phenotypes and genotypes of 123 IRD probands, 69 males and 54 females, mean age 41 (IQR, 54-30) years, disease onset at 13 (IQR, 27.25-5) years. Thirty-three patients out of 123 (26.8%) were Africans (North/Northwest Africa), 21 (17.1%) Asians, 19 (15.4%) Americans (South/Central America) and 50 (40.7%) Europeans (Eastern Europe). Retinitis pigmentosa was the most represented phenotype (56%), followed by cone dystrophy (11%) and Leber congenital amaurosis (7%), while ABCA4 was the most frequently mutated gene (18%), followed by USH2A (9%) and RPGR (5%). About ABCA4 variants found in Stargardt disease, macular and cone dystrophies were predominant in Asian (42%) and European (21%) patients. The most represented inheritance pattern was autosomal recessive, while a higher frequency of homozygous patients versus compound heterozygotes as compared to previous studies on Italian IRD patients was evidenced, reflecting a possible higher frequency of inbreeding marriages. Conclusion: Though limited by the relatively low number of patients, the present paper paints a picture of the clinical and genetic features of IRD patients from understudied ethnic groups referred to Italian specialized hospitals and extended the epidemiological studies on underrepresented world regional areas.

Genetic characteristics of 234 Italian patients with macular and cone/cone-rod dystrophy.

Two-hundred and thirty-four Italian patients with a clinical diagnosis of macular, cone and cone-rod dystrophies (MD, CD, and CRD) were examined using next-generation sequencing (NGS) and gene sequencing panels targeting a specific set of genes, Sanger sequencing and-when necessary-multiplex ligation-dependent probe amplification (MLPA) to diagnose the molecular cause of the aforementioned diseases. When possible, segregation analysis was performed in order to confirm unsolved cases. Each patient's retinal phenotypic characteristics were determined using focal and full-field ERGs, perimetry, spectral domain optical coherence tomography and fundus autofluorescence. We identified 236 potentially causative variants in 136 patients representing the 58.1% of the total cohort, 43 of which were unpublished. After stratifying the patients according to their clinical suspicion, the diagnostic yield was 62.5% and 53.8% for patients with MD and for those with CD/CRD, respectively. The mode of inheritance of all cases confirmed by genetic analysis was 70% autosomal recessive, 26% dominant, and 4% X-linked. The main cause (59%) of both MD and CD/CRD cases was the presence of variants in the ABCA4 gene, followed by variants in PRPH2 (9%) and BEST1 (6%). A careful morpho-functional evaluation of the phenotype, together with genetic counselling, resulted in an acceptable diagnostic yield in a large cohort of Italian patients. Our study emphasizes the role of targeted NGS to diagnose MDs, CDs, and CRDs, as well as the clinical usefulness of segregation analysis for patients with unsolved diagnosis.

RPE65-Associated Retinopathies in the Italian Population: A Longitudinal Natural History Study.

Purpose: To investigate the course of inherited retinal degenerations (IRD) due to mutations in the RPE65 gene. Methods: This longitudinal multicentric retrospective chart-review study was designed to collect best corrected visual acuity (BCVA), Goldman visual field, optical coherence tomography (OCT), and electroretinography (ERG) measurements. The data, including imaging, were collected using an electronic clinical research form and were reviewed at a single center to improve consistency. Results: From an overall cohort of 60 Italian patients with RPE65-associated IRD, 43 patients (mean age, 27.8 ± 19.7 years) were included and showed a mean BCVA of 2.0 ± 1.0 logMAR. Time-to-event analysis revealed a median age of 33.8 years and 41.4 years to reach low vision and blindness based on BCVA, respectively. ERG (available for 34 patients) showed undetectable responses in most patients (26; 76.5%). OCT (available for 31 patients) revealed epiretinal membranes in five patients (16.1%). Central foveal thickness significantly decreased with age at a mean annual rate of -0.6%/y (P = 0.044). We identified 43 different variants in the RPE65 gene in the entire cohort. Nine variants were novel. Finally, to assess genotype-phenotype correlations, patients were stratified according to the number of RPE65 loss-of-function (LoF) alleles. Patients without LoF variants showed significantly (P < 0.05) better BCVA compared to patients with one or two LoF alleles. Conclusions: We described the natural course of RPE65-associated IRD in an Italian cohort showing for the first time a specific genotype-phenotype association. Our findings can contribute to a better management of RPE65-associated IRD patients.

Treatment of Advanced Coats' Disease With Combination Therapy of Laser Photocoagulation, Intravitreal Ranibizumab, and Sub-Tenon Methylprednisolone Acetate.

PURPOSE: To investigate the efficacy of combination therapy with laser photocoagulation, intravitreal ranibizumab, and sub-Tenon methylprednisolone acetate in patients presenting with advanced Coats' disease. METHODS: This was a retrospective analysis of 16 patients who underwent laser photocoagulation combined with intravitreal ranibizumab and sub-Tenon methylprednisolone acetate between 2008 and 2017. The primary outcome was anatomic success and the secondary outcomes were globe preservation and final visual acuity. RESULTS: The average age at surgery was 5.12 ± 2.7 years (range: 3 to 10 years). The mean follow-up time was 45.43 ± 29.01 months (range: 12 to 108 months). Of the 16 patients (16 eyes) reviewed, 6 patients had stage 3A and 10 patients had stage 3B Coats' disease. The mean number of applications was 10 (range: 4 to 18). Globe preservation was achieved in all patients. Final visual acuity outcomes were satisfactory: 20/20 to 20/50 in 2 patients, 20/60 to 20/100 in 1 patient, and 20/200 or worse in 13 patients. CONCLUSIONS: Intravitreal ranibizumab used in combination with laser photocoagulation and sub-Tenon methylprednisolone acetate could be an effective treatment option for patients with advanced Coats' disease. The combined therapy achieved anatomical success, globe preservation, and reasonable visual acuity outcomes. [J Pediatr Ophthalmol Strabismus. 2022;59(3):187-191.].

Comparative analysis of visual outcomes of multifocal and monofocal intraocular lenses in congenital cataract surgery.

PURPOSE: To assess the impact on visual development of multifocal vs monofocal intraocular lenses (IOLs) implantation in children after congenital cataract surgery. SETTING: Ophthalmology Department, Bambino Gesù Children's Hospital, Rome, Italy. DESIGN: Retrospective interventional consecutive case series. METHODS: Records of 56 eyes of 43 pediatric patients who underwent congenital cataract surgery with phacoaspiration and simultaneous implantation of the IOL younger than 1 year were reviewed. Corrected distance visual acuity (CDVA), refractive error, and ocular motility disorders were evaluated at follow-up of greater than 4 years. RESULTS: 32 multifocal (18 unilateral, Group A and 14 bilateral, Group B) and 24 monofocal (12 unilateral, Group C and 12 bilateral, Group D) IOLs were implanted. Mean follow-up was 6.67 years. Mean CDVA of the eyes with multifocal IOLs was 0.75 ± 0.46 logMAR in unilateral cataract surgery and 0.34 ± 0.25 logMAR in bilateral ones; with monofocal IOLs was 0.71 ± 0.52 logMAR in unilateral and 0.53 ± 0.43 logMAR in bilateral ones. No statistically significant difference in the CDVA between Groups A and B and Groups C and D were recorded. Final mean spherical equivalent was -3.88 ± 4.73 diopters (D); in Group A, it was -2.74 ± 4.22 D, in Group C was -1.08 ± 1.45 D, in Group B was -4.82 ± 4.64 D, and in Group D was -6.81 ± 4.61 D. The difference was statistically significant between Groups B and D (P = .01), but not between Groups A and C (P = .14). 26 patients (60.4%) showed postoperative strabismus. Surgical correction occurred more in patients with multifocal IOLs implanted (P = .038). CONCLUSIONS: Multifocal IOLs did not show significant advantages in visual development in children after congenital cataract extraction younger than 1 year when compared with monofocal IOLs.

Dexamethasone Intravitreal Implant (Ozurdex) in Paediatric Patients with Non-infectious Intermediate Uveitis and Related Cystoid Macular Oedema: Evaluation of Macular Morphology and Function with Six-month Follow-up; a Deeper Role of MfERG?

PURPOSE: To evaluate the efficacy of Ozurdex implant by analyzing macular morphology and function in pediatric uveitis and related cystoid macular edema (CMO). METHODS: Main outcomes were visual acuity, mfERG and photopic ERG response, and central macular thickness. Mean values recorded at each time-point were compared to baseline and correlations between functional and anatomical parameters were evaluated. RESULTS: Resolution of intraocular inflammation and CMO was achieved in all eyes 1 month after implant without procedure or drug-related complications. Mean visual acuity and mfERG amplitude improved showing a statistically significant difference to baseline values for the first 4 months. Mean central macular thickness showed a statistically significant reduction for all follow-up time. Photopic ERG did not vary significantly. Statistically significant correlation was found between trends of visual acuity, central macular thickness, and mfERG responses. CONCLUSION: Correlation found between macular morphology and function confirms the efficacy of Ozurdex in pediatric uveitis.

Care Pathway of RPE65-Related Inherited Retinal Disorders from Early Symptoms to Genetic Counseling: A Multicenter Narrative Medicine Project in Italy.

PURPOSE: Timely detection and multidisciplinary management of RPE65-related inherited retinal disorders (IRDs) can significantly improve both disease management and patient care. Thus, this Narrative Medicine (NM) project aimed to investigate the evolution of the care pathway and the expectations on genetic counseling and gene therapy by patients, caregivers, and healthcare professionals. PATIENTS AND METHODS: This project was conducted between July and December 2020, involving five Italian eye clinics specialized in IRDs, targeted pediatric and adult patients, their caregivers, attending retinologists and multidisciplinary healthcare professionals. Narratives and parallel charts, together with a sociodemographic survey, were collected through the project webpage. In-depth interviews were conducted with Patient Association (PA) members and multidisciplinary healthcare professionals. All data were entered into the Nvivo Software for coding and analysis. RESULTS: Three pediatric and five adult patients with early-onset RPE65-related IRDs as well as eight caregivers were enrolled; 11 retinologists globally wrote 27 parallel charts; in-depth interviews were done with five multidisciplinary healthcare professionals and one PA member. Early diagnosis remains challenging, and patients reported to have changed up to 10 healthcare professionals before accessing their specialized center. Despite the oftentimes lack of awareness of patients and caregivers on the purpose of genetic testing, participants generally consider gene therapy as a therapeutic chance and a historic breakthrough for the management of RPE65-related IRDs. Well-organized networks to support the patient's referral to specialized centers - as well as a proper communication of the clinical and genetic diagnosis and the multidisciplinary approach - emerge as crucial aspects in facilitating an early diagnosis and management and a timely initiation of the rehabilitation pathway. CONCLUSION: The project investigated the RPE65-related IRDs care pathway while integrating the different perspectives involved through NM. The analysis explored the patient's pathway in Italy and confirmed the need for a well-organized network and multidisciplinary care while highlighting several preliminary areas of improvement in the management of RPE65-related IRDs.

Blue Cone Monochromatism with Foveal Hypoplasia Caused by the Concomitant Effect of Variants in OPN1LW/OPN1MW and GPR143 Genes.

Blue cone monochromatism (BCM) is an X-linked recessive cone dysfunction disorder caused by mutations in the OPN1LW/OPN1MW gene cluster, encoding long (L)- and middle (M)-wavelength-sensitive cone opsins. Here, we report on the unusual clinical presentation of BCM caused by a novel mutation in the OPN1LW gene in a young man. We describe in detail the phenotype of the proband, and the subclinical morpho-functional anomalies shown by his carrier mother. At a clinical level, the extensive functional evaluation demonstrated in the proband the M/L cone affection and the sparing of S-cone function, distinctive findings of BCM. Interestingly, spectral-domain optical coherence tomography showed the presence of foveal hypoplasia with focal irregularities of the ellipsoid layer in the foveal area, reported to be associated with some cases of cone-rod dystrophy and achromatopsia. At a molecular level, we identified the novel mutation c.427T > C p.(Ser143Pro) in the OPN1LW gene and the common missense mutation c.607T > C (p.Cys203Arg) in the OPN1MW gene. In addition, we discovered the c.768-2_769delAGTT splicing variant in the GPR143 gene. To our knowledge, this is the first case of foveal hypoplasia in a BCM patient and of mild clinical affection in a female carrier caused by the concomitant effect of variants in OPN1LW/OPN1MW and GPR143 genes, thus as the result of the simultaneous action of two independent genetic defects.

Inner Macular Changes in Fellow Eye of Patients With Unilateral Idiopathic Epiretinal Membrane.

Purpose: We evaluated a series of fellow eyes (FEs) in patients affected by unilateral idiopathic epiretinal membrane (IERM) with spectral-domain optical coherence tomography (SD-OCT) and OCT angiography (OCT-A) to determine if a previous defect in the inner retina is present before the mechanical damage to the inner limiting membrane (ILM) caused by posterior vitreous detachment. Methods: In patients with IERM (N = 39), ganglion cell layer (GCL) thickness in FEs was assessed with SD-OCT; in a subgroup (N = 25) the vessel density (VD) at the superficial (SCP) and deep capillary plexus (DCP) was assessed with swept-source OCT-A (SS-OCT-A). These values were then compared with 30 age-matched healthy control eyes (CEs). The statistical analyses used SPSS software version 15.0 (SPSS, Inc., Chicago, IL, USA). Data collected underwent 1-way ANOVA. A level of P < 0.05 was accepted as statistically significant. Results: The GCL thickness in the FEs was significantly lower than in CEs, with a significant thinning in all sectors except temporal ones (mean P < 0.001, superior P = 0.0002, superonasal P < 0.001, inferonasal P < 0.001, and inferior P = 0.002). The VD was significantly lower in the FEs in all sectors of SCP (mean P = 0.009, inner ring P = 0.028, and outer ring P = 0.007). Conclusions: GCL and SCP are significantly reduced in the FEs. These data suggest that a vascular defect in the SCP could cause a cellular loss in the inner retina that may determine the cascade events leading to the IERM proliferation; the diagnosis in a preclinical phase could provide a treatment strategy to prevent the progression of the disease.

Ocular manifestations and viral shedding in tears of pediatric patients with coronavirus disease 2019: a preliminary report.

PURPOSE: To evaluate ocular manifestations and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) prevalence in the tears of children with coronavirus disease 2019 (COVID-19). METHODS: A total of 27 pediatric patients with confirmed COVID-19 infection hospitalized from March 16 to April 15, 2020, at the Bambino Gesù Children's Hospital were enrolled in the study. At admission, all patients showed ocular manifestations. Reverse transcriptase-polymerase chain reaction from nasopharyngeal and conjunctival swabs were performed every 2-3 days before discharge. RESULTS: Of the 27 patients, 4 (15%) were asymptomatic, 15 (56%) showed respiratory symptoms, and 8 (30%) had gastrointestinal symptoms. At admission, nasopharyngeal swabs were positive for COVID-19 in all patients; on the second swabs, 7 children (26%) tested negative, and 20 remained positive for COVID-19. Ocular manifestations consistent with mild viral conjunctivitis were observed in 4 patients (15%). At first conjunctival swab, 3 patients (11%), 1 symptomatic and 2 asymptomatic for ocular infection, had positive findings for COVID-19; 2 became negative on the second test and 1 on the third. CONCLUSIONS: In our study cohort, ocular manifestations of COVID-19 seem to have had a milder clinical course in pediatric patients than in adults. Despite the low prevalence and rapid regression of viral presence in the conjunctiva, SARS-CoV-2 transmission through tears may be possible, even in patients without apparent ocular involvement.