Optical coherence tomography biomarkers in MYO7A-inherited retinal dystrophy: longitudinal study in pediatric patients.

PURPOSE: This study aims to answer a key question: is MYO7A-inherited retinal dystrophy (MYO7A-IRD) a photoreceptor-first or retinal pigment epithelium-first disease? A second aim was to determine the most useful biomarkers to monitor disease progression in pediatric patients with Usher syndrome type 1B (USH1) secondary to MYO7A mutation. METHODS: Fifty-two eyes from 26 patients with genetically-confirmed MYO7A-IRD underwent swept-source optical coherence tomography (SS-OCT). Structural abnormalities were evaluated and correlated with follow-up time and best corrected visual acuity (BCVA). All patients were evaluated at baseline and after ≥ 40 months of follow-up. RESULTS: The mean (SD) patient age was 9.92 (± 4.1) years. Mean follow-up time was 43 (± 3.2) months. At the final evaluation, the most common qualitative abnormalities in the subfoveal area were alterations in the photoreceptor outer segments (76.9% of eyes) and in the interdigitation zone (IZ) (80.8%). The presence of cystoid macular edema at baseline was independently associated with worse BCVA at the final assessment (increase in LogMAR estimate = 0.142; t(45.00) = 2.78, p = 0.009). The mean width of the ellipsoid and interdigitation zones decreased significantly (by 668 µm and 278 µm, respectively; both p < 0.001). CONCLUSION: This study shows that disruption of the photoreceptor outer segments and the IZ are the first alterations detected by SS-OCT in the early phases of MYO7A-IRD. These data highlight the potential value of measuring the width of the ellipsoid and IZ to evaluate disease progression. These findings also demonstrate the utility of monitoring for the emergence of cystic lesions as biomarkers of worse visual prognosis in patients with MYO7A-IRD.

Optical coherence tomography for the screening of anterior chamber inflammation in paediatric patients diagnosed with juvenile idiopathic arthritis.

OBJECTIVES: To evaluate the effectiveness of the anterior segment optical coherence tomography (AS-OCT) for the screening of anterior uveitis in children diagnosed with juvenile idiopathic arthritis (JIA). METHODS: A cross-sectional, observational, non-randomised study was conducted in JIA patients younger than 18 years. All patients underwent anterior segment (AS-OCT) and macular OCT. RESULTS: A total of 300 eyes of 150 patients diagnosed with JIA were included; 74% were females, and mean age was 11.12 ± 3.51 years old (range 4.13-18.60). In the slit-lamp examination, anterior uveitis was diagnosed in 16 eyes. In the AS-OCT, anterior uveitis was suspected in 27 eyes; cells were detected in 27 eyes and retrokeratic precipitates in 5 eyes. Sensitivity was 0.94 and specificity was 0.96, positive predictive value was 0.59 and negative predictive value was 0.99, and Kappa-Cohen index was 0.71. CONCLUSIONS: AS-OCT could be considered for the screening of anterior segment uveitis in children diagnosed with JIA.

A practical approach to uveitis screening in children with juvenile idiopathic arthritis.

BACKGROUND: Juvenile idiopathic arthritis (JIA)-associated uveitis typically presents as a silent chronic anterior uveitis and can lead to blindness. Adherence to current screening guidelines is hampered by complex protocols which rely on the knowledge of specific JIA characteristics. The Multinational Interdisciplinary Working Group for Uveitis in Childhood identified the need to simplify screening to enable local eye care professionals (ECPs), who carry the main burden, to screen children with JIA appropriately and with confidence. METHODS: A consensus meeting took place in January 2023 in Barcelona, Spain, with an expert panel of 10 paediatric rheumatologists and 5 ophthalmologists with expertise in paediatric uveitis. A summary of the current evidence for JIA screening was presented. A nominal group technique was used to reach consensus. RESULTS: The need for a practical but safe approach that allows early uveitis detection was identified by the panel. Three screening recommendations were proposed and approved by the voting members. They represent a standardised approach to JIA screening taking into account the patient's age at the onset of JIA to determine the screening interval until adulthood. CONCLUSION: By removing the need for the knowledge of JIA categories, antinuclear antibody positivity or treatment status, the recommendations can be more easily implemented by local ECP, where limited information is available. It would improve the standard of care on the local level significantly. The proposed protocol is less tailored to the individual than the 'gold standard' ones it references and does not aim to substitute those where they are being used with confidence.

Bilateral choroidal osteoma: long-term follow-up of secondary choroidal neovascularization in a child using antiangiogenic therapy.

Choroidal osteoma is a rare condition, and its treatment is not well established, especially in the pediatric population, where use of antiangiogenics for choroidal neovascularization is poorly studied. Few studies have reported the long-term follow-up of pediatric patients with bilateral choroidal osteomas. We report the case of a girl who was diagnosed at the age of 3, with the appearance of bilateral secondary choroidal neovascularization, and has been under strict observation for 12 years. The effectiveness of antiangiogenic agents as a long-term therapeutic option for secondary choroidal neovascularization in pediatric patients with symptomatic choroidal osteomas is discussed.

INTRARETINAL HUMAN AMNIOTIC MEMBRANE AFTER MACULAR HOLE REPAIR.

PURPOSE: To describe a unique complication of macular hole repair surgery using a subretinal human amniotic membrane plug. METHODS: Retrospective, interventional case report. RESULTS: A 71-year-old man presented with a chronic full-thickness macular hole in his left eye. Conventional 23-gauge pars plana vitrectomy with internal limiting membrane peeling and implantation of a subretinal human amniotic membrane plug was performed. In the postoperative period, centripetal growth of external retinal layers was observed under the plug. Six months after the surgery, the human amniotic membrane plug was completely integrated into the retina. CONCLUSION: This is the first reported case of intraretinal integration of a human amniotic membrane plug after macular hole repair surgery.

Spontaneous Regression of Choroidal Neovascularization in a Girl with Rubella Retinopathy.

Rubella retinopathy is usually a benign disorder with low impact on visual acuity. However, choroidal neovascularization can occur in these patients threatening their vision. We report the case of a 6-year-old girl with rubella retinopathy who developed a neovascular membrane and was successfully managed with observation. Decision to treat or observe in these patients must be carefully weighed, with both options being valid depending mainly on the location of the neovascular complex.

Retinal findings in pediatric patients with Usher syndrome Type 1 due to mutations in MYO7A gene.

PURPOSE: To describe retinal alterations detected by swept-source optical coherence tomography (SS-OCT) in paediatric patients with Usher syndrome type 1 (USH1) and to compare these findings to previously published reports. METHODS: Thirty-two eyes from 16 patients (11 males and 5 females) with a genetic diagnosis of USH1 because of MYO7A mutations underwent SS-OCT. Patients ranged in age from 4 to 17 years (mean, 11,13 ± 4,29). The subfoveal and macular area were analysed with SS-OCT at 1050 nm using 12 radial scans of 12.0 mm. Structural abnormalities were evaluated and correlated with best-corrected visual acuity (BCVA). RESULTS: The most common qualitative retinal abnormality was external layer damage in macular area. Specific alterations included external limiting membrane loss/disruption (27 eyes; 84.4%), disruption of the Myoid zone (27 eyes; 84.4%); Ellipsoid zone disruption (28 eyes; 87.5%), and loss of the outer segments (29 eyes; 90.6%). The damage of the retinal pigment epithelium was divided according to the loss of the different layers: phagosome zone (30 eyes; 93.8%), melanosome zone (29 eyes; 90.6%) and mitochondria zone (0 eyes; 0%). The presence of cystoid macular oedema (CMO) was significantly correlated with alterations in photoreceptors. Disruption or absence of the myoid and ellipsoid zones of the photoreceptors were the only variables independently associated with decreased BCVA. CONCLUSIONS: The findings of this study suggest that the physiopathologic basis of early-stage Usher syndrome (USH) may be changes in the outer retinal layer, particularly the photoreceptors, which in turn may cause alterations-such as CMO-in the inner retinal layers. Accordingly, monitoring the condition of photoreceptors during follow-up may be advisable for the early detection of pathologic changes.

Macular Hole After Poppers (Alkyl Nitrate) Inhalation in a Child.

The authors present the first case of macular hole (MH) after a single inhalation of poppers. A 13-year-old girl presented with vision loss in the left eye (OS). Pediatric and neurology exams were normal. Funduscopy revealed bilateral papilledema and yellow foveal spot OS. Optic neuritis was diagnosed and treated. Due to foveal alteration, optical coherence tomography was performed, and MH was diagnosed. Twenty-three-gauge pars plana vitrectomy, peeling of the internal limiting membrane, and SF6 exchange were performed. Postoperatively, vision restoration and MH closure were observed. Although MH mechanism in the poppers context is unknown, the classic surgery is effective. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:897-900.].

Progression of retinal pigmentation mimicking unilateral retinitis pigmentosa after bilateral pars planitis: a case report.

BACKGROUND: To report our findings in a young patient with unilateral retinitis pigmentosa (RP)-like appearance who developed pigmentary changes in his left retina after an episode of bilateral pars planitis. CASE PRESENTATION: A 17-year-old man presented with 6 months of blurry vision in both eyes. He was diagnosed with bilateral pars planitis. Progressive, intraretinal bone crepuscule pigmentation developed in his left retina during the following three months. An electroretinogram showed subnormal response only in the left eye, suggesting the diagnosis of unilateral pseudoRP. CONCLUSION: An inflammatory disease like pars planitis can accelerate the pigmentation of the retina and mimic a RP in young patients. Causes of pseudoRP may be considered, especially in those rare cases with unilateral affection.

Anterior iris-claw intraocular lens implantation for the management of nontraumatic ectopia lentis: long-term outcomes in a paediatric cohort.

PURPOSE: To report the feasibility and long-term safety of lensectomy and iris-claw intraocular lens (IOL) implantation to treat children with severe ectopia lentis in a paediatric tertiary hospital. METHODS: Prospective cohort study of 21 eyes from 12 patients with severe ectopia lentis and visual acuity <20/63. All eyes underwent 23-gauge pars plana vitrectomy, lensectomy, iridectomy and Artisan IOL implantation in the anterior chamber with iris-claw enclavation via pars plana. Mean age at surgery was 8.0 ± 5.3 yo (range 3-17 years). A full ophthalmologic examination including best-corrected visual acuity (BCVA), biomicroscopy, intraocular pressure (IOP) measurement, fundus evaluation and central endothelial cell count (cECC) was performed pretreatment, at 3 months' postsurgery, and every 6 months thereafter. Ultrasound biomicroscopy (UBM) was performed 12 months after surgery. RESULTS: Mean follow-up was 39.3 ± 13.0 months. Best-corrected visual acuity (BCVA) (mean ± SD) improved from 0.91 ± 0.29 logMar preoperatively to 0.18 ± 0.23 logMar at final follow-up (p < 0.0001). Mean distance from the endothelium to the anterior IOL surface after surgery was 3.11 ± 0.61 mm. Postsurgically, cECC loss was 5.04% ± 9.58% with an annual cECC loss rate of 3.16% ± 4.46%. One patient developed IOL dislocation and retinal detachment after severe ocular contusion requiring vitrectomy, IOL refixation and gas tamponade. Another patient developed cystoid macular oedema, managed with intravitreal dexamethasone. CONCLUSION: This technique is both feasible and effective to manage severe ectopia lentis in children. Lifetime ophthalmic follow-up including cECC measurement, IOL position monitoring and fundus examination is mandatory in these patients.

Incidence and distribution of paravascular lamellar holes and their relationship with macular retinoschisis in highly myopic eyes using spectral-domain oct.

The purpose of the study is to determine the incidence and distribution of paravascular lamellar holes (PLH) around retinal vessels in highly myopic eyes and their relationship with macular retinoschisis (MR). We examined 306 eyes of 178 patients with high myopia, performing multiple scans of the posterior pole within the retinal vascular arcades using spectral-domain OCT. Type of staphyloma was determined. PLH were divided into three groups: holes only (group 1), holes extending below vessels (group 2), and holes in an area of paravascular retinoschisis (group 3). OCT showed that 96/306 eyes (31.4 %) had PLH mainly along the infero-temporal arcade (39.9 %). Type V and IX staphylomas had a higher proportion of PLH in the infero-temporal arcade than other staphylomas. Group 3 eyes presented higher rates of myopia and staphyloma. MR was detected in 10/27 eyes (37 %) in Group 3, but only in 2/33 eyes (6.1 %) in Group 1. No MR was found in Group 2. PLH are relatively common in highly myopic eyes and mainly distributed in the inferior temporal arcade. Findings from this descriptive study suggest that distribution of PLH might be related to the type of staphyloma. Further studies are needed to evaluate the relevance of PLH in the pathogenesis of MR.

Next generation sequencing uncovers a missense mutation in COL4A1 as the cause of familial retinal arteriolar tortuosity.

OBJECTIVES: Our aim was to determine the molecular cause of autosomal dominant familial retinal arteriolar tortuosity (FRAT) in a family with three affected subjects. MATERIAL AND METHODS: Ophthalmologic evaluation included determination of best-corrected visual acuity (BCVA), slit-lamp and dilated fundus inspection, applanation tonometry, fundus photography, and fluorescein retinal angiography (FA). Molecular methods included whole exome sequencing analysis and Sanger sequencing validation of putative causal mutation in DNA from affected individuals. RESULTS: Typical signs of familial retinal arteriolar tortuosity were observed in all three patients. Exome sequencing identified a heterozygous c.1528G > A (p. Gly510Arg) mutation in COL4A1. Sanger sequencing confirmed that all three patients harbored the same pathogenetic mutation in COL4A1. The p. Gly510Arg variant in COL4A1 was absent in DNA from an available unaffected daughter, from a set of control alleles, and from publicly available databases. CONCLUSIONS: The molecular basis of familial retinal arteriolar tortuosity was identified for the first time, thus expanding the human phenotypes linked to COL4A1 mutations. Interestingly, the COL4A1 p.Gly510Arg mutation has been previously identified in a family with HANAC (Hereditary Angiopathy with Nephropathy, Aneurysm and Cramps), a multisystemic disease featuring retinal arteriolar tortuosity. No cerebral, neurologic, renal, cardiac or vascular anomalies were recognized in the pedigree described here. These data indicate that identical mutations in COL4A1 can originate both eye-restricted and systemic phenotypes.

Usefulness of adalimumab in the treatment of refractory uveitis associated with juvenile idiopathic arthritis.

PURPOSE: To assess the efficacy and safety of adalimumab in patients with juvenile idiopathic arthritis (JIA) and associated refractory uveitis. DESIGN: Multicenter, prospective case series. METHODS: Thirty-nine patients (mean [SD] age of 11.5 [7.9] years) with JIA-associated uveitis who were either not responsive to standard immunosuppressive therapy or intolerant to it were enrolled. Patients aged 13-17 years were treated with 40 mg of adalimumab every other week for 6 months and those aged 4-12 years received 24 mg/m(2) body surface. RESULTS: Inflammation of the anterior chamber (2.02 [1.16] versus 0.42 [0.62]) and of the posterior segment (2.38 [2.97] versus 0.35 [0.71] decreased significantly between baseline and the final visit (P < 0.001). The mean (SD) macular thickness at baseline was 304.54 (125.03) µ and at the end of follow-up was 230.87 (31.12) µ (P < 0.014). Baseline immunosuppression load was 8.10 (3.99) as compared with 5.08 (3.76) at the final visit (P < 0.001). The mean dose of corticosteroids also decreased from 0.25 (0.43) to 0 (0.02) mg (P < 0.001). No significant side effects requiring discontinuation of therapy were observed. CONCLUSION: Adalimumab seems to be an effective and safe treatment for JIA-associated refractory uveitis and may reduce steroid requirement.

Intraocular lens dislocation after whole-body vibration.

We present 2 cases of intraocular lens (IOL) dislocation that appeared shortly after the patients exercised on a vibration platform. The first patient was a 71-year-old woman who presented with lens subluxation in her right eye and a complete posterior IOL dislocation in her left eye. The second case was a 62-year-old woman who presented with unilateral IOL dislocation within the capsular bag in her right eye. Timing from IOL implantation to dislocation was approximately 6 years and 4 years, respectively. Pars plana vitrectomy with removal of the dislocated IOL was performed in both patients. Whole-body vibration training has become increasingly popular as a form of exercise training. It reportedly may provide benefits in physical function and in some diseases, especially in older people. However, evidence-based protocols ensuring safety and efficacy in this population are lacking. We discuss vibration as a cause of late IOL dislocation.

Combined retinal detachment and candida chorioretinitis.

To report a case of slowly progressive traction and rhegmatogenous retinal detachment after successfully managed candida chorioretinitis. A 44-year-old immunocompromised woman was treated with voriconazole for fungal chorioretinitis. Six months after onset she developed a combined retinal detachment. Slow progression of retinal detachment was observed and vitrectomy was performed. The macular area remained attached and visual acuity was maintained. Ophthalmologists should be aware of this unusual complication after the resolution of active candida chorioretinitis.