This Issue at a Glance

Abstract

Lally et al (p. 679) performed next-generation sequencing on 101 conjunctival melanomas to evaluate targetable mutations and molecular genetic pathways. They assessed BRAF mutation status alone in 5 melanomas, whereas a larger panel of 592 genes was used in 68 melanomas. The 4 most commonly identified mutations were in NF1 (39%), BRAF (31%), NRAS (26%), and ATRX (25%) genes, with 71% of ATRX mutations occurring alongside an additional NF1 mutation. The ATRX mutation was associated with loss of ATRX protein expression and alternative lengthening of telomeres (ALT) in both intraepithelial and invasive tumors, suggesting that an ATRX mutation is an early event in conjunctival melanoma progression. The NRAS mutation was associated with increased risk of metastasis and death. The findings confirm the high frequency of BRAF, NRAS, ATRX, and NF1 mutations in conjunctival melanoma, and suggest that the ALT pathway may have prognostic value. Grisafe II et al (p. 668) assessed how race, ethnicity, and age influenced the associations between visual field loss (VFL) and vision-specific quality of life (VSQOL). Analysis of 17 071 adults revealed that a 5-point reduction in task and wellbeing scores was associated with mild-to-moderate VFL for Latinos and Chinese Americans and with moderate-to-severe VFL for Black Americans. These differences reached statistical significance when comparing Latinos and Black Americans. Among participants aged 65 years and older, there was a 0.487-point greater loss in VSQOL scores for driving difficulties with every 1 dB of mean deviation in VFL compared with younger participants. The authors conclude that race and ethnicity significantly modified the relationship between VFL and VSQOL, with Latinos and Chinese Americans reporting a greater change in VSQOL than Black Americans for the same level of VFL. Zekavat et al (p. 694) analyzed genomic, electronic health record, and retinal OCT data from 44 823 Europeans to characterize the epidemiologic and genetic associations between age-related macular degeneration (AMD) and retinal layer thicknesses. Photoreceptor segment (PS) thinning was observed across all ages, whereas retinal pigment epithelium (RPE) and Bruch’s membrane (BM) complex thickening started after 57 years of age. Each standard deviation of PS thinning and RPE-BM complex thickening was associated with incident AMD. Genetic variants that increase risk of AMD were significantly associated with decreased PS thickness, whereas a bimodal association was detected with RPE-BM complex thickness. Locus-specific analyses identified potential mechanistic roles of AMD risk alleles at CFH and ARMS2/HTRA1 on PS thinning and at SYN3/TIMP3 on RPE-BM complex thickening. The authors suggest that PS thinning may precede RPE-BM complex thickening in AMD by decades and could serve as an early-stage biomarker for future AMD development. Singer et al (p. 605) prospectively assessed the safety and efficacy of the 0.19-mg fluocinolone acetonide (FAc) intravitreal implant in patients with diabetic macular edema (DME). Analysis of 202 eyes from 159 patients revealed a mean central subfield thickness change of –60.69 μm and a mean best-corrected visual acuity change of +3.61 letters compared with baseline at 36 months after FAc implantation. Median frequency of DME-related treatments was reduced by 70.5% from 3.4 treatments to 1 treatment per year, and 25.53% of eyes remained rescue free at 36 months. Mean intraocular pressure (IOP) remained relatively stable throughout the study and IOP-related procedures were infrequent. An IOP response of < 25 mmHg after steroid therapy was highly predictive of a similar IOP response at the end of the study. The authors conclude that the FAc implant provides effective control of macular edema in DME with a low incidence of IOP-related safety concerns. Tsui et al (p. 661) and Bui et al (p. 721) prospectively compared 6- and 12-month outcomes of uveitic macular edema in 216 patients treated with methotrexate or mycophenolate mofetil (MMF). The analysis by Tsui et al revealed that treatment with methotrexate or MMF resulted in similar improvements in macular thickness at 6 and 12 months. At 12 months, resolution of macular edema occurred in 37% of eyes on methotrexate and 60% of eyes on MMF, whereas for those who switched treatments at 6 months it occurred in 47% of eyes on methotrexate and 55% of eyes on MMF. Additionally, the subanalysis by Bui et al found no difference in corticosteroid exposure or in the time to reach a corticosteroid-sparing prednisone dosage between the methotrexate and MMF groups. The authors suggest that methotrexate and MMF are equally efficacious in treating noninfectious uveitis but note that approximately half of the patients still had persistent edema after treatment.