Comprehensive genomic diagnosis of inherited retinal and optical nerve disorders reveals hidden syndromes and personalized therapeutic options.

PURPOSE: In the era of precision medicine, genomic characterization of blind patients is critical. Here, we evaluate the effects of comprehensive genetic analysis on the etiologic diagnosis of potentially hereditary vision loss and its impact on clinical management. METHODS: We studied 100 non-syndromic and syndromic Spanish patients with a clinical diagnosis of blindness caused by alterations on the retina, choroid, vitreous and/or optic nerve. We used a next-generation sequencing (NGS) panel (OFTALMOgenics™), developed and validated within this study, including up to 362 genes previously associated with these conditions. RESULTS: We identified the genetic cause of blindness in 45% of patients (45/100). A total of 28.9% of genetically diagnosed cases (13/45) were syndromic and, of those, in 30.8% (4/13) extraophthalmic features had been overlooked and/or not related to visual impairment before genetic testing, including cases with Mainzer-Saldino, Bardet-Biedl, mucolipidosis and MLCRD syndromes. In two additional cases-syndromic blindness had been proposed before, but not specifically diagnosed, and one patient with Heimler syndrome had been misdiagnosed as an Usher case before testing. 33.3% of the genetically diagnosed patients (15/45) had causative variants in genes targeted by clinical trials exploring the curative potential of gene therapy approaches. CONCLUSION: Comprehensive genomic testing provided clinically relevant insights in a large proportion of blind patients, identifying potential therapeutic opportunities or previously undiagnosed syndromes in 42.2% of the genetically diagnosed cases (19/45).

Implantation of a Trifocal Intraocular Lens in High Myopic Eyes with Nasal-Inferior Staphyloma.

PURPOSE: To assess visual outcomes in high myopic eyes with nasal-inferior staphyloma implanted with a pseudophakic trifocal intraocular lens (IOL). METHODS: We retrospectively analyzed the visual outcomes of 50 eyes of 45 patients who had cataract surgery after AT LISA trifocal IOL implantation. Twenty-five eyes diagnosed with posterior staphyloma (nasal-inferior, type IV and V), and 25 eyes as long eyes. Uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA) values were used to assess the efficacy and safety of the surgery. Refraction and defocus curves were also evaluated at 6 months. RESULTS: No intra- or post-operative problems occurred during the 6 months of follow-up. After the surgery, the mean Snellen decimal UDVA ranged from 0.50 to 1.00, and CDVA from 0.60 to 1.00 for both groups. CDVA was 0.91 and 0.74 for the long eye and nasal-inferior staphyloma groups, respectively. Efficacy and safety indexes were 1.22 and 1.32 for the long eye, and 1.26 and 1.43 for the nasal-inferior staphyloma group, respectively. All eyes of both groups showed a postoperative spherical equivalent within ±1.00D. The long eye group showed the highest percentage of spherical equivalent between -0.13D and +0.13D (56%) and the nasal-inferior staphyloma group was between -0.51D and -0.14D (40%). CONCLUSION: The outcomes of the present study show that a trifocal IOL provides good visual acuity in high myopic eyes, being worse for nasal-inferior staphyloma eyes. The degree of tilt of the macular plane is related with the expected visual acuity.

Metallothionein polymorphisms in a Northern Spanish population with neovascular and dry forms of age-related macular degeneration.

BACKGROUND: To elucidate the potential role of single nucleotide polymorphisms (SNPs) in the metallothionein (MT) genes in Northern Spanish patients with age-related macular degeneration (AMD). METHODS: A total of 130 unrelated Northern Spanish natives diagnosed with AMD (46 dry, 35 neovascular, and 49 mixed) and 96 healthy controls, matched by age and ethnicity, were enrolled in a case-control study. DNA was isolated from peripheral blood and genotyped for 14 SNPs located at 5 MT genes (MT1A: rs11076161, rs 11640851, rs8052394, and rs7196890; MT1B: rs8052334, rs964372, and rs7191779; MT1M: rs2270836 and rs9936741; MT2A: rs28366003, rs1610216, rs10636, and rs1580833; MT3: rs45570941) using TaqMan probes. The association study was performed using the HaploView 4.0 software. RESULTS: The allelic and genotypic frequencies analysis revealed that rs28366003 at MT2A gene is significantly associated with dry AMD. The frequency of genotype AG was significantly higher in dry AMD than in control cases (p = 2.65 × 10-4; AG vs. AA) conferring more than ninefold increased risk to dry AMD (OR = 9.39, 95% CI: 2.11-41.72), whereas the genotype AA confers disease protection (OR = 0.82, 95% CI: 0.71-0.95). No statistically significant differences were observed between AMD subjects and controls in the rest of the 14 SNPs analyzed. CONCLUSIONS: The present study is the first to investigate the potential association of SNPs at MT genes with susceptibility to AMD. We found a significant association of SNP rs28366003 at MT2A gene with susceptibility to the dry form of AMD in a Northern Spanish population.

Intravitreal bevacizumab associated with photodynamic therapy in a case of polypoidal choroidal vasculopathy associated with choroidal nevus: A case report.

RATIONALE: Report the clinical findings and management of a case of polypoidal choroidal vasculopathy associated with choroidal nevus which received combination therapy. PATIENT CONCERNS: Decreased visual acuity in a woman with polypoidal choroidal vasculopathy and choroidal nevus. DIAGNOSES: Polypoidal choroidal vasculopathy and choroidal nevus. INTERVENTIONS: The initial visual acuity was 0.5. After the first treatment with photodynamic therapy, exudation and bleeding appeared around the lesion. After this, the patient received 3 doses of intravitreal bevacizumab. OUTCOMES: After treatment with combination therapy, visual acuity, clinical and imaging findings improved, with no recurrence of exudation and bleeding. LESSONS: Intravitreal bevacizumab as an adjunctive treatment after photodynamic therapy is a good option for patients with polypoidal choroidal vasculopathy associated with choroidal nevus.