Invasive squamous cell carcinomas and precursor lesions on UV-exposed epithelia demonstrate concordant genomic complexity in driver genes.

Although squamous cell carcinomas (SCC) are the most frequent human solid tumor at many anatomic sites, the driving molecular alterations underlying their progression from precursor lesions are poorly understood, especially in the context of photodamage. Therefore, we used high-depth, targeted next-generation sequencing (NGS) of RNA and DNA from routine tissue samples to characterize the progression of both well- (cutaneous) and poorly (ocular) studied SCCs. We assessed 56 formalin-fixed paraffin-embedded (FFPE) cutaneous lesions (n = 8 actinic keratosis, n = 30 carcinoma in situ [CIS], n = 18 invasive) and 43 FFPE ocular surface lesions (n = 2 conjunctival/corneal intraepithelial neoplasia, n = 20 CIS, n = 21 invasive), from institutions in the US and Brazil. An additional seven cases of advanced cutaneous SCC were profiled by hybrid capture-based NGS of >1500 genes. The cutaneous and ocular squamous neoplasms displayed a predominance of UV-signature mutations. Precursor lesions had highly similar somatic genomic landscapes to SCCs, including chromosomal gains of 3q involving SOX2, and highly recurrent mutations and/or loss of heterozygosity events affecting tumor suppressors TP53 and CDKN2A. Additionally, we identify a novel molecular subclass of CIS with RB1 mutations. Among TP53 wild-type tumors, human papillomavirus transcript was detected in one matched pair of cutaneous CIS and SCC. Amplicon-based whole-transcriptome sequencing of select 20 cutaneous lesions demonstrated significant upregulation of pro-invasion genes in cutaneous SCCs relative to precursors, including MMP1, MMP3, MMP9, LAMC2, LGALS1, and TNFRSF12A. Together, ocular and cutaneous squamous neoplasms demonstrate similar alterations, supporting a common model for neoplasia in UV-exposed epithelia. Treatment modalities useful for cutaneous SCC may also be effective in ocular SCC given the genetic similarity between these tumor types. Importantly, in both systems, precursor lesions possess the full complement of major genetic changes seen in SCC, supporting non-genetic drivers of invasiveness.

Diamond burr superficial keratectomy in the treatment of visually-significant anterior corneal lesions.

PURPOSE: To evaluate the efficacy and safety of diamond burr superficial keratectomy in the treatment of visually-significant anterior corneal lesions. METHODS: A retrospective review of 23 eyes (23 patients). Pre- and postoperative visual acuities and refractions, slit-lamp biomicroscopic findings, and the incidence of recurrence of disease after keratectomy were studied. RESULTS: Nineteen eyes had map-dot-fingerprint basement membrane dystrophy and 4 had Salzmann's nodular degeneration. All patients presented with decreased vision, as well as varying degrees of glare, halos, and monocular diplopia. Postoperative follow-up ranged from 3 to 39 months (mean 10.6 months), and no recurrence of the original disease occurred within this period. This procedure improved the best-corrected visual acuity from 20/36 (LogMar 0.250) to 20/24 (LogMar 0.076) by LogMar statistical evaluation (p<0.001) and caused a statistically non-significant (p=0.232) myopic change in the mean refractive spherical equivalent (-0.36 diopter +/- SD 2.28 preoperatively to -0.71 +/- 2.26 postoperatively). Glare and monocular diplopia were subjectively reduced or eliminated in all patients. One patient had mild anterior stromal haze which decreased the bestcorrected visual acuity from 20/25 to 20/30. CONCLUSION: Diamond burr superficial keratectomy appears to be an effective and safe method of removing visually-significant anterior corneal opacities.

Femtosecond laser-assisted lamellar keratoplasty.

Lamellar keratoplasty consists of transplanting partial-thickness donor cornea onto a complementary recipient bed. Manual lamellar dissection is technically very difficult, time-consuming, and imprecise. Also, the manually-dissected lamellar interface often has topographical irregularities that may optically degrade the best-corrected visual acuity. The femtosecond clinical laser (IntraLase FS Laser, Irvine, CA) is a recent innovation that can be programmed to produce bladeless, precise lamellar cuts at any depth with accompanying trephination cuts for both anterior and posterior lamellar transplantation. Posterior laser cuts may be used to assist in deep lamellar endothelial keratoplasty or Descemet's stripping automated endothelial keratoplasty.

Diamond burr superficial keratectomy in the treatment of visually-significant anterior corneal lesions / Ceratectomia superficial com broca de diamante no tratamento de lesões anteriores da córnea

PURPOSE: To evaluate the efficacy and safety of diamond burr superficial keratectomy in the treatment of visually-significant anterior corneal lesions. METHODS: A retrospective review of 23 eyes (23 patients). Pre- and postoperative visual acuities and refractions, slit-lamp biomicroscopic findings, and the incidence of recurrence of disease after keratectomy were studied. RESULTS: Nineteen eyes had map-dot-fingerprint basement membrane dystrophy and 4 had Salzmann's nodular degeneration. All patients presented with decreased vision, as well as varying degrees of glare, halos, and monocular diplopia. Postoperative follow-up ranged from 3 to 39 months (mean 10.6 months), and no recurrence of the original disease occurred within this period. This procedure improved the best-corrected visual acuity from 20/36 (LogMar 0.250) to 20/24 (LogMar 0.076) by LogMar statistical evaluation (p<0.001) and caused a statistically non-significant (p=0.232) myopic change in the mean refractive spherical equivalent (-0.36 diopter ± SD 2.28 preoperatively to -0.71 ± 2.26 postoperatively). Glare and monocular diplopia were subjectively reduced or eliminated in all patients. One patient had mild anterior stromal haze which decreased the bestcorrected visual acuity from 20/25 to 20/30. CONCLUSION: Diamond burr superficial keratectomy appears to be an effective and safe method of removing visually-significant anterior corneal opacities.

OBJETIVO: Avaliar a eficácia e segurança da ceratectomia superficial com broca de diamante no tratamento das lesões anteriores da córnea. MÉTODOS: Foi realizado estudo retrospectivo de 23 olhos de 23 pacientes. Foram avaliados acuidade visual e refração pré e pós-operatório, biomicroscopia e incidência de recorrência da doença após ceratectomia. RESULTADOS: Dos 23 olhos avaliados, 19 olhos apresentavam distrofia da membrana basal (map-dot-fingerprint) e 4 degeneração nodular de Salzmann. Todos os pacientes apresentavam diminuição da acuidade visual, assim como graus variados de ofuscamento, halos e diplopia monocular. O seguimento pós-operatório variou entre 3 e 39 meses (média de 10,6 meses) e não houve recorrência da doença original nesse período. O procedimento melhorou a acuidade visual com melhor correção de 20/36 (LogMar 0,250) para 20/24 (LogMar 0,076) com p<0,001. Em relação as mudanças refracionais não houve significância (p=0,232) sendo o equivalente esférico pré-operatório de - 0,36 ± 2,28DE e pós-operatório de -0,71 ± 2,26DE. As queixas de ofuscamento e diplopia monocular diminuíram ou foram eliminadas em todos os pacientes. Apenas 1 paciente apresentou nubécula no estroma anterior com diminuição da acuidade visual com melhor correção de 20/25 para 20/30. CONCLUSÃO: Ceratectomia superficial com broca de diamante parece ser método efetivo e seguro para remover opacidades anteriores de córnea.

Femtosecond laser-assisted lamellar keratoplasty / Transplante lamelar auxiliado pelo laser de fentosegundo

Lamellar keratoplasty consists of transplanting partial-thickness donor cornea onto a complementary recipient bed. Manual lamellar dissection is technically very difficult, time-consuming, and imprecise. Also, the manually-dissected lamellar interface often has topographical irregularities that may optically degrade the best-corrected visual acuity. The femtosecond clinical laser (IntraLase FS LaserTM, Irvine, CA) is a recent innovation that can be programmed to produce bladeless, precise lamellar cuts at any depth with accompanying trephination cuts for both anterior and posterior lamellar transplantion. Posterior laser cuts may be used to assist in deep lamellar endothelial keratoplasty or Descemet's stripping automated endothelial keratoplasty.

A ceratoplastia lamelar consiste em transplante de espessura parcial da córnea doadora em um leito receptor complementar. A dissecção lamelar manual é técnica de difícil realização, imprecisa e que demanda tempo. Além disso, a interface lamelar freqüentemente apresenta irregularidade topográfica que pode comprometer a acuidade visual final. O laser clínico "femtosecond" (IntraLase FS LaserTM, Irvine, CA) é uma recente inovação que pode ser utilizado para produzir cortes lamelares precisos em qualquer profundidade da córnea, acompanhados de cortes verticais tanto para transplantes lamelares anteriores como posteriores sem a utilização de lâminas. Os cortes posteriores podem ser utilizados para a realização de ceratoplastia endotelial lamelar profunda ou ceratoplastia endotelial com remoção da membrana de Descemet.