Long-term Outcomes of Surgeries for Retinal Detachment Secondary to Parasitic or Viral Infectious Retinitis.

PURPOSE: This study sought to compare the long-term outcomes of surgeries for retinal detachment (RD) secondary to viral or parasitic infectious retinitis. METHODS: A total of 47 eyes that received pars plana vitrectomy with or without scleral buckling due to RD secondary to polymerase chain reaction-proven viral (cytomegalovirus, varicella zoster virus, and herpes zoster virus) or parasitic (toxoplasma and toxocara) retinitis from October 1, 2006, to June 30, 2023, in a single medical center were retrospectively enrolled. RESULTS: Mean follow-up period was 59.03 ± 55.24 months in viral retinitis and 34.80 ± 33.78 months in parasitic retinitis after primary reattachment surgery. During follow-up, nine eyes (24.3%) with viral retinitis and five eyes (50.0%) with parasitic retinitis developed retinal redetachment. Visual acuity success at final follow-up was achieved in 19 eyes (51.4%) with viral retinitis and six eyes (60.0%) with parasitic retinitis (p = 0.64). The incidence of retinal redetachment during the 1st postoperative year was significantly higher in parasitic retinitis compared with viral retinitis (crude incidence, 0.21 vs. 0.85; p = 0.02). Hazard ratio analysis adjusted for age and sex showed 4.58-fold (95% confidence interval, 1.22-17.27; p = 0.03) increased risk of retinal redetachment in parasitic retinitis compared with viral retinitis during the 1st postoperative year. Tamponade with silicone oil and preoperative diagnostic vitrectomy were associated with significantly decreased risk of retinal redetachment in patients with parasitic retinitis. CONCLUSIONS: Compared with RD secondary to viral retinitis, RD secondary to parasitic retinitis showed higher incidence of retinal redetachment during the 1st postoperative year. Tamponade with silicone oil and preoperative diagnostic vitrectomy were associated with significantly decreased risk of retinal redetachment in patients with parasitic retinitis.

Next-Generation Sequencing of Vitreoretinal Lymphoma by Vitreous Liquid Biopsy: Diagnostic Potential and Genotype/Phenotype Correlation.

Purpose: To determine the diagnostic potential of next-generation sequencing (NGS) in vitreous samples, analyze genotype-phenotype characteristics, and compare NGS of matched vitreous and brain samples in patients with associated central nervous system lymphoma (CNSL). Methods: A total of 32 patients suspected of vitreoretinal lymphoma (VRL) who underwent diagnostic vitrectomy and NGS were included in this retrospective observational case-series. Fresh vitreous specimens from diagnostic vitrectomy of VRL-suspected patients underwent NGS using a custom panel targeting 747 candidate genes for lymphoma. They also underwent malignancy cytology, interleukin (IL)-10/IL-6, immunoglobulin heavy chain (IGH)/immunoglobulin kappa light chain (IGK) monoclonality testing. MYD88 L265P mutation was examined from anterior chamber tap samples. The diagnosis of VRL was made based on typical clinical characteristics for VRL, as well as malignant cytology, IGH/IGK clonality, or IL-10/IL-6 > 1. Sensitivity and specificity of NGS were compared with conventional diagnostic tests. Brain tissues suspected of lymphoma were collected by stereotactic biopsy and underwent NGS. Genetic variations detected in NGS of vitreous and brain tissue specimens were compared. Results: The sensitivity values for cytology, IL-10/IL-6 > 1, clonality assays for IGH and IGK, MYD88 L265P detection in anterior chamber tap samples, and vitreous NGS were 0.23, 0.83, 0.68, 0.79, 0.67, and 0.85, with specificity values of 1.00, 0.83, 0.50, 0.25, 0.83, and 0.83, respectively. The sensitivity (0.85) of vitreous NGS was the highest compared to other conventional diagnostic tests for VRL. The most common mutations were MYD88 (91%), CDKN2A (36%), PIM1 (32%), IGLL5 (27%), and ETV6 (23%). Although several gene alterations demonstrated heterogeneity between the brain and eyes, some common mutational profiles were observed in matched vitreous and brain samples. Conclusions: Overall, NGS of the vitreous demonstrated high sensitivity among conventional diagnostic tests. VRL and CNSL appeared to have both shared and distinct genetic variations, which may suggest site-specific variations from a common origin.

CRISPR/Cas9 mediated specific ablation of vegfa in retinal pigment epithelium efficiently regresses choroidal neovascularization.

The CRISPR/Cas9 system easily edits target genes in various organisms and is used to treat human diseases. In most therapeutic CRISPR studies, ubiquitously expressed promoters, such as CMV, CAG, and EF1α, are used; however, gene editing is sometimes necessary only in specific cell types relevant to the disease. Therefore, we aimed to develop a retinal pigment epithelium (RPE)-specific CRISPR/Cas9 system. We developed a CRISPR/Cas9 system that operates only in retinal pigment epithelium (RPE) by expressing Cas9 under the RPE-specific vitelliform macular dystrophy 2 promoter (pVMD2). This RPE-specific CRISPR/pVMD2-Cas9 system was tested in human retinal organoid and mouse model. We confirmed that this system works specifically in the RPE of human retinal organoids and mouse retina. In addition, the RPE-specific Vegfa ablation using the novel CRISPR-pVMD2-Cas9 system caused regression of choroidal neovascularization (CNV) without unwanted knock-out in the neural retina in laser-induced CNV mice, which is a widely used animal model of neovascular age-related macular degeneration. RPE-specific Vegfa knock-out (KO) and ubiquitous Vegfa KO were comparable in the efficient regression of CNV. The promoter substituted, cell type-specific CRISPR/Cas9 systems can be used in specific 'target cell' therapy, which edits genes while reducing unwanted off- 'target cell' effects.

Evaluation of blood vessel network formation and visual field defect in optic disc melanocytoma.

AIM: To investigate the association between visual field defects and blood vessel network (BVN) formation in optic disc melanocytomas (ODMs) using optical coherence tomography angiography (OCTA). METHODS: Single-centre, retrospective case series of 32 eyes of 32 patients with ODM, in which eyes were divided into two groups based on complete and incomplete BVN formations. RESULTS: OCTA revealed incomplete BVN formation in 16 of 32 ODMs. The location of BVN absence corresponded to the location of hypofluorescence from fluorescein angiography (FA) in 12 (75%) and to the location of visual field defect in 13 (81%) ODMs in the incomplete BVN group. Perimetric indices were significantly worse in the incomplete BVN group than in the complete BVN group. Linear regression of mean deviation (MD) and Visual Field Index (VFI) on the area of BVN absence were statistically significant (p=0.01 and p=0.003, respectively), whereas linear regressions of MD and VFI on the tumour area were not statistically significant (both p=0.09) in the incomplete BVN group. CONCLUSION: The location of BVN absence within ODMs corresponded to the location of visual field defect and the location of FA hypofluorescence. Visual field defect was more severe in the incomplete BVN group than in the complete BVN group. Visual field defect was more significantly associated with the area of BVN absence than the tumour area.

Short-Term Outcomes of the First in Vivo Gene Therapy for RPE65-Mediated Retinitis Pigmentosa.

Here, we report early treatment outcomes of gene therapy for early onset retinitis pigmentosa (RP) (Leber congenital amaurosis) associated with biallelic RPE65 mutation in a 30-year-old female patient. Initially, her visual acuity (VA) was 20/200, and her visual field (VF) was severely constricted to the center in the left eye. Her electroretinography showed nearly extinct signals. Full-field stimulus threshold test (FST) revealed diminished dark-adapted light sensitivity. Voretigene neparvovec-rzyl (VN) is the first in vivo viral gene therapy agent to be approved. At 3 months after subretinal injection of VN in the left eye, VA, VF, and FST showed sustained improvement. She did not exhibit any signs of adverse effects from the treatment. Gene therapy for RP proved to be an effective and safe treatment in an advanced case of RPE65-associatied early onset RP.

Exacerbation of Granular Corneal Dystrophy Type 2 After Small Incision Lenticule Extraction.

PURPOSE: To report the outcome of unilateral small incision lenticule extraction (SMILE) in a patient with granular corneal dystrophy type 2 (GCD2). METHODS: Slit-lamp photography and Fourier domain optical coherence tomography were used to document the clinical course and appearance of the corneas in a patient with genetically determined GCD2 who underwent unilateral SMILE in the right eye. RESULTS: Slit-lamp examination of a 23-year-old woman revealed 2 faint opacities at the surgical interface approximately 2 months after the SMILE procedure had been performed on her right eye. Nine and 3 typical GCD2 deposits located immediately beneath the Bowman layer were observed in the right and left corneas, respectively. Over time, the deposits at the interface increased in size, density, and number in the right eye. Fourier domain optical coherence tomography performed 33 months after the SMILE procedure revealed deposits at the SMILE interface that were distinct from those located immediately beneath the Bowman layer. The severity of disease exacerbation was less in this patient than what is typically observed in others who have undergone laser-assisted in situ keratomileusis or photorefractive keratectomy. CONCLUSIONS: SMILE is contraindicated in patients with GCD2, as are other corneal refractive surgical procedures. This case highlights the importance of genetic testing before the performance of refractive corneal procedures-especially for patients with corneal opacities on preoperative slit-lamp examination or a family history of corneal disease compatible with that of a corneal dystrophy.

Clinical Outcomes of Small Incision Lenticule Extraction in Myopia: Study of Vector Parameters and Corneal Aberrations.

PURPOSE: To investigate clinical outcomes of small incision lenticule extraction (SMILE) including vector parameters and corneal aberrations in myopic patients. METHODS: This retrospective, observational case series included 57 eyes (29 patients) that received treatment for myopia using SMILE. Visual acuity measurement, manifest refraction, slit-lamp examination, autokeratometry, corneal topography, and evaluation of corneal wavefront aberration were performed preoperatively and at 1 and 3 months after surgery. We analyzed the safety, efficacy, vector parameters, and corneal aberrations at 3 months after surgery. RESULTS: Preoperatively, mean manifest refraction spherical equivalent refraction was -4.94 ± 1.94 D (range, -8.25 to 0 diopters [D]), and the cylinder was -1.14 ± 0.82 D (range, -3 to 0 D). Mean manifest refraction spherical equivalent improved to -0.10 ± 0.23 D at 3 months postoperatively, when uncorrected distance visual acuity was 20 / 20 or better in 55 (96%) eyes. The linear regression model of target induced astigmatism vector versus surgically induced astigmatism vector exhibited slopes and coefficients (R²) of 0.9618 and 0.9748, respectively (y = 0.9618x + 0.0006, R² = 0.9748). While total corneal root mean square higher order aberrations, coma and trefoil showed statistically significant increase, spherical aberration did not show statistically significant change after SMILE. CONCLUSIONS: SMILE has proven to be effective and safe for correcting myopia and astigmatism. We showed that SMILE did not induce spherical aberrations. A small increase in postoperative corneal higher order aberration may be associated with increase in coma and trefoil.