Reduction of foveal bulges and other anatomical changes in fellow eyes of patients with unilateral idiopathic macular hole without vitreomacular pathologic changes.

PURPOSE: To compare the foveal characteristics in fellow eyes (FE) of patients with unilateral idiopathic macular hole without vitreomacular pathologic changes with eyes of healthy controls. METHODS: Forty-seven FE and 52 eyes of 52 age- and sex-matched healthy controls were studied. Quantitative assessment of the dome-shaped appearance of the hyperreflective lines that represent external limiting membrane (ELM_bulge) and inner outer segment junctions (IS/OS_bulge) were made by optical coherence tomography (OCT) images. Inner retinal complex thickness (IRCT) was quantitatively assessed at 1000 and 2000 µm of the foveal center in nasal and temporal quadrants. Presence of alterations in the inner retinal outer layers and central foveal thickness (CFT) were also analyzed. RESULTS: Significantly lower ELM_bulge (p < 0.0001; Mann-Whitney test) and IS/OS_bulge (p < 0.001; student t test) and higher cases with COST alterations, expressed as a diffuse line (p < 0.006; Chi2 test) were found in FE than control eyes. IRCT were significantly reduced in FE at all the studied locations when comparing to control eyes (p < 0.05; student t test), maintaining anatomical proportionality among locations. CONCLUSION: FE without pathologic vitreomacular interactions seems to present some central cone alterations that may be related to other causes than vitreomacular traction.

New COL6A6 variant detected by whole-exome sequencing is linked to break points in intron 4 and 3'-UTR, deleting exon 5 of RHO, and causing adRP.

PURPOSE: This study aimed to test a newly devised cost-effective multiplex PCR assay for the molecular diagnosis of autosomal dominant retinitis pigmentosa (adRP), as well as the use of whole-exome sequencing (WES) to detect disease-causing mutations in adRP. METHODS: Genomic DNA was extracted from peripheral blood lymphocytes of index patients with adRP and their affected and unaffected family members. We used a newly devised multiplex PCR assay capable of amplifying the genetic loci of RHO, PRPH2, RP1, PRPF3, PRPF8, PRPF31, IMPDH1, NRL, CRX, KLHL7, and NR2E3 to molecularly diagnose 18 index patients with adRP. We also performed WES in affected and unaffected members of four families with adRP in whom a disease-causing mutation was previously not found. RESULTS: We identified five previously reported mutations (p.Arg677X in the RP1 gene, p.Asp133Val and p.Arg195Leu in the PRPH2 gene, and p.Pro171Leu and p.Pro215Leu in the RHO gene) and one novel mutation (p.Val345Gly in the RHO gene) representing 33% detection of causative mutations in our adRP cohort. Comparative WES analysis showed a new variant (p.Gly103Arg in the COL6A6 gene) that segregated with the disease in one family with adRP. As this variant was linked with the RHO locus, we sequenced the complete RHO gene, which revealed a deletion in intron 4 that encompassed all of exon 5 and 28 bp of the 3'-untranslated region (UTR). CONCLUSIONS: The novel multiplex PCR assay with next-generation sequencing (NGS) proved effective for detecting most of the adRP-causing mutations. A WES approach led to identification of a deletion in RHO through detection of a new linked variant in COL6A6. No pathogenic variants were identified in the remaining three families. Moreover, NGS and WES were inefficient for detecting the complete deletion of exon 5 in the RHO gene in one family with adRP. Carriers of this deletion showed variable clinical status, and two of these carriers had not previously been diagnosed with RP.

Eye movements in patients with post-COVID condition.

Eye movement control is impaired in some neurological conditions, but the impact of COVID-19 on eye movements remains unknown. This study aims to investigate differences in oculomotor function and pupil response in individuals who suffer post-COVID-19 condition (PCC) with cognitive deficits. Saccades, smooth pursuit, fixation, vergence and pupillary response were recorded using an eye tracker. Eye movements and pupil response parameters were computed. Data from 16 controls, 38 COVID mild (home recovery) and 19 COVID severe (hospital admission) participants were analyzed. Saccadic latencies were shorter in controls (183 ± 54 ms) than in COVID mild (236 ± 83 ms) and COVID severe (227 ± 42 ms) participants (p = 0.017). Fixation stability was poorer in COVID mild participants (Bivariate Contour Ellipse Area of 0.80 ± 1.61°2 vs 0.36 ± 0.65 °2 for controls, p = 0.019), while percentage of pupil area reduction/enlargement was reduced in COVID severe participants (39.7 ± 12.7%/31.6 ± 12.7% compared to 51.7 ± 22.0%/49.1 ± 20.7% in controls, p < 0.015). The characteristics of oculomotor alterations found in PCC may be useful to understand different pathophysiologic mechanisms.

Vitrectomy without face-down posturing for idiopathic macular holes.

PURPOSE: To report the results of vitrectomy with internal limiting membrane peeling and C3F8 tamponade for macular hole without postoperative face-down posturing in 208 eyes. METHODS: The study included 208 eyes on an uncontrolled retrospective review, undergoing pars plana vitrectomy with trypan blue-assisted internal limiting membrane peeling and C3F8 tamponade, without subsequent face-down posturing. All patients were followed-up at 1 day, 1 week, 3 months, and 12 months postoperatively. Biomicroscopy and optical coherence tomography were used to assess macular hole closure at 1 day, 1 week, 3 months, and 12 months postoperatively. Pre- and postoperative visual acuity by Snellen chart was compared. RESULTS: In 208 eyes with idiopathic macular hole, preoperative mean visual acuity was 20/200 and final visual acuity was 20/40 (P = 0.00017). Anatomic macular hole closure rate was 81.3%. CONCLUSION: In agreement with published studies, combined phacovitrectomy without face-down posturing after macular hole surgery seems effective and safe, showing anatomical improvement and favorable best-corrected visual acuity. Isolating the macula from vitreous fluid with a large long-lasting gas-fill may render postoperative posturing unnecessary. Eliminating face-down posturing may increase patient acceptance and compliance.

Mutant PRPF8 Causes Widespread Splicing Changes in Spliceosome Components in Retinitis Pigmentosa Patient iPSC-Derived RPE Cells.

Retinitis pigmentosa (RP) is a rare, progressive disease that affects photoreceptors and retinal pigment epithelial (RPE) cells with blindness as a final outcome. Despite high medical and social impact, there is currently no therapeutic options to slow down the progression of or cure the disease. The development of effective therapies was largely hindered by high genetic heterogeneity, inaccessible disease tissue, and unfaithful model organisms. The fact that components of ubiquitously expressed splicing factors lead to the retina-specific disease is an additional intriguing question. Herein, we sought to correlate the retinal cell-type-specific disease phenotype with the splicing profile shown by a patient with autosomal recessive RP, caused by a mutation in pre-mRNA splicing factor 8 (PRPF8). In order to get insight into the role of PRPF8 in homeostasis and disease, we capitalize on the ability to generate patient-specific RPE cells and reveal differentially expressed genes unique to RPE cells. We found that spliceosomal complex and ribosomal functions are crucial in determining cell-type specificity through differential expression and alternative splicing (AS) and that PRPF8 mutation causes global changes in splice site selection and exon inclusion that particularly affect genes involved in these cellular functions. This finding corroborates the hypothesis that retinal tissue identity is conferred by a specific splicing program and identifies retinal AS events as a framework toward the design of novel therapeutic opportunities.

Bilateral choroidal neovascularization associated with optic nerve head drusen treated by antivascular endothelial growth factor therapy.

OBJECTIVE: To report a good clinical outcome in a patient with bilateral choroidal neovascularization (CNV) associated with optic nerve head drusen (ONHD) treated with intravitreal ranibizumab injection. METHODS: A 12-year-old girl was referred for loss of right eye vision detected in a routine check-up. Best-corrected visual acuity (BCVA) was hand movements in the right eye and 0.9 in the left eye. Funduscopy revealed the presence of superficial and buried bilateral ONHD, which was confirmed by ultrasonography and computed tomography, and the study was completed with perimetry. The presence of bilateral CNV, active in the right eye, was observed and subsequently confirmed using fluorescein angiography and optical coherence tomography. RESULTS: Treatment with two consecutive injections of intravitreal ranibizumab resulted in inactivation of the neovascular membrane with subretinal fluid reabsorption and improved right eye BCVA. After 12 months' follow-up, this was 20/60 and stable. CONCLUSION: Although there are no published studies of safety in children, antiangiogenic therapy for CNV secondary to ONHD may be useful and safe. A search of the literature produced only one previously reported case of ONHD-associated CNV treated with antivascular endothelial growth factor alone.

Temporal branch retinal vein occlusion secondary to a racemose hemangioma.

PURPOSE: To describe a case of venous thrombosis secondary to unilateral racemose hemangioma (RH). METHODS: Biomicroscopic examination, fluorescein angiography, and optical coherence tomography were used. The patient was a 12-year-old girl who was seen for progressive loss of visual acuity in the left eye. RESULTS: Examination revealed venous thrombosis in the superior temporal vein area in the context of arteriovenous malformation (AVM). Treatment with intravitreal triamcinolone (4 mg) resulted in anatomic and functional improvement. CONCLUSION: This was an exceptional case of branch retinal vein occlusion secondary to RH in a girl without known risk factors for venous obstruction. The obstruction was attributable to the large-caliber superior temporal artery, which, on forming a loop in the region of the venous branch, produced an obstruction of venous branch blood flow.