Xrn2 substrate mapping identifies torpedo loading sites and extensive premature termination of RNA pol II transcription.

The exonuclease torpedo Xrn2 loads onto nascent RNA 5'-PO4 ends and chases down pol II to promote termination downstream from polyA sites. We report that Xrn2 is recruited to preinitiation complexes and "travels" to 3' ends of genes. Mapping of 5'-PO4 ends in nascent RNA identified Xrn2 loading sites stabilized by an active site mutant, Xrn2(D235A). Xrn2 loading sites are approximately two to 20 bases downstream from where CPSF73 cleaves at polyA sites and histone 3' ends. We propose that processing of all mRNA 3' ends comprises cleavage and limited 5'-3' trimming by CPSF73, followed by handoff to Xrn2. A similar handoff occurs at tRNA 3' ends, where cotranscriptional RNase Z cleavage generates novel Xrn2 substrates. Exonuclease-dead Xrn2 increased transcription in 3' flanking regions by inhibiting polyA site-dependent termination. Surprisingly, the mutant Xrn2 also rescued transcription in promoter-proximal regions to the same extent as in 3' flanking regions. eNET-seq revealed Xrn2-mediated degradation of sense and antisense nascent RNA within a few bases of the TSS, where 5'-PO4 ends may be generated by decapping or endonucleolytic cleavage. These results suggest that a major fraction of pol II complexes terminates prematurely close to the start site under normal conditions by an Xrn2-mediated torpedo mechanism.

Alternative RNA structures formed during transcription depend on elongation rate and modify RNA processing.

Most RNA processing occurs co-transcriptionally. We interrogated nascent pol II transcripts by chemical and enzymatic probing and determined how the "nascent RNA structureome" relates to splicing, A-I editing and transcription speed. RNA folding within introns and steep structural transitions at splice sites are associated with efficient co-transcriptional splicing. A slow pol II mutant elicits extensive remodeling into more folded conformations with increased A-I editing. Introns that become more structured at their 3' splice sites get co-transcriptionally excised more efficiently. Slow pol II altered folding of intronic Alu elements where cryptic splicing and intron retention are stimulated, an outcome mimicked by UV, which decelerates transcription. Slow transcription also remodeled RNA folding around alternative exons in distinct ways that predict whether skipping or inclusion is favored, even though it occurs post-transcriptionally. Hence, co-transcriptional RNA folding modulates post-transcriptional alternative splicing. In summary, the plasticity of nascent transcripts has widespread effects on RNA processing.

Selective inhibition of CDK7 reveals high-confidence targets and new models for TFIIH function in transcription.

CDK7 associates with the 10-subunit TFIIH complex and regulates transcription by phosphorylating the C-terminal domain (CTD) of RNA polymerase II (RNAPII). Few additional CDK7 substrates are known. Here, using the covalent inhibitor SY-351 and quantitative phosphoproteomics, we identified CDK7 kinase substrates in human cells. Among hundreds of high-confidence targets, the vast majority are unique to CDK7 (i.e., distinct from other transcription-associated kinases), with a subset that suggest novel cellular functions. Transcription-associated factors were predominant CDK7 substrates, including SF3B1, U2AF2, and other splicing components. Accordingly, widespread and diverse splicing defects, such as alternative exon inclusion and intron retention, were characterized in CDK7-inhibited cells. Combined with biochemical assays, we establish that CDK7 directly activates other transcription-associated kinases CDK9, CDK12, and CDK13, invoking a "master regulator" role in transcription. We further demonstrate that TFIIH restricts CDK7 kinase function to the RNAPII CTD, whereas other substrates (e.g., SPT5 and SF3B1) are phosphorylated by the three-subunit CDK-activating kinase (CAK; CCNH, MAT1, and CDK7). These results suggest new models for CDK7 function in transcription and implicate CAK dissociation from TFIIH as essential for kinase activation. This straightforward regulatory strategy ensures CDK7 activation is spatially and temporally linked to transcription, and may apply toward other transcription-associated kinases.

Control of RNA Pol II Speed by PNUTS-PP1 and Spt5 Dephosphorylation Facilitates Termination by a "Sitting Duck Torpedo" Mechanism.

Control of transcription speed, which influences many co-transcriptional processes, is poorly understood. We report that PNUTS-PP1 phosphatase is a negative regulator of RNA polymerase II (Pol II) elongation rate. The PNUTS W401A mutation, which disrupts PP1 binding, causes genome-wide acceleration of transcription associated with hyper-phosphorylation of the Spt5 elongation factor. Immediately downstream of poly(A) sites, Pol II decelerates from >2 kb/min to <1 kb/min, which correlates with Spt5 dephosphorylation. Pol II deceleration and Spt5 dephosphorylation require poly(A) site recognition and the PNUTS-PP1 complex, which is in turn necessary for transcription termination. These results lead to a model for termination, the "sitting duck torpedo" mechanism, where poly(A) site-dependent deceleration caused by PNUTS-PP1 and Spt5 dephosphorylation is required to convert Pol II into a viable target for the Xrn2 terminator exonuclease. Spt5 and its bacterial homolog NusG therefore have related functions controlling kinetic competition between RNA polymerases and the termination factors that pursue them.

Dynamic turnover of paused Pol II complexes at human promoters.

Paused RNA polymerase II (Pol II) that piles up near most human promoters is the target of mechanisms that control entry into productive elongation. Whether paused Pol II is a stable or dynamic target remains unresolved. We report that most 5' paused Pol II throughout the genome is turned over within 2 min. This process is revealed under hypertonic conditions that prevent Pol II recruitment to promoters. This turnover requires cell viability but is not prevented by inhibiting transcription elongation, suggesting that it is mediated at the level of termination. When initiation was prevented by triptolide during recovery from high salt, a novel preinitiated state of Pol II lacking the pausing factor Spt5 accumulated at transcription start sites. We propose that Pol II occupancy near 5' ends is governed by a cycle of ongoing assembly of preinitiated complexes that transition to pause sites followed by eviction from the DNA template. This model suggests that mechanisms regulating the transition to productive elongation at pause sites operate on a dynamic population of Pol II that is turning over at rates far higher than previously suspected. We suggest that a plausible alternative to elongation control via escape from a stable pause is by escape from premature termination.

Effects of Transcription Elongation Rate and Xrn2 Exonuclease Activity on RNA Polymerase II Termination Suggest Widespread Kinetic Competition.

The torpedo model of transcription termination asserts that the exonuclease Xrn2 attacks the 5'PO4-end exposed by nascent RNA cleavage and chases down the RNA polymerase. We tested this mechanism using a dominant-negative human Xrn2 mutant and found that it delayed termination genome-wide. Xrn2 nuclease inactivation caused strong termination defects downstream of most poly(A) sites and modest delays at some histone and U snRNA genes, suggesting that the torpedo mechanism is not limited to poly(A) site-dependent termination. A central untested feature of the torpedo model is that there is kinetic competition between the exonuclease and the pol II elongation complex. Using pol II rate mutants, we found that slow transcription robustly shifts termination upstream, and fast elongation extends the zone of termination further downstream. These results suggest that kinetic competition between elongating pol II and the Xrn2 exonuclease is integral to termination of transcription on most human genes.

Metastasis of Lung Adenocarcinoma to the Lacrimal Sac.

The authors report an unusual case of lung adenocarcinoma metastasis to the lacrimal sac. A 61-year-old woman with stage IV non-small cell lung cancer presented with left facial pain and epiphora. She was found to have an elevated tear meniscus associated with a firm, fixed medial canthal mass. Orbital imaging demonstrated nodular enlargement of the lacrimal drainage apparatus. Biopsy of the lacrimal sac was performed, and it revealed a metastatic lung adenocarcinoma. The patient received targeted radiation therapy to the lacrimal sac, and her dose of maintenance chemotherapy was increased. The patient's symptoms have since improved. This case of lung cancer involving the lacrimal sac highlights the importance of thorough oncologic surveillance, even with respect to locations atypical for metastatic spread.

Histopathologic Observations of Eyes in Exenterated Orbits After Neoadjuvant Intra-Arterial Cytoreductive Chemotherapy for Adenoid Cystic Carcinoma of the Lacrimal Gland.

PURPOSE: To assess whether exenteration specimens obtained after neoadjuvant intra-arterial cytoreductive chemotherapy (IACC) for adenoid cystic carcinoma of the lacrimal gland demonstrate significant ocular histopathologic alterations that might preclude future pursuit of globe-preserving therapy. METHODS: Retrospective histopathologic analysis of globes in IACC-treated exenteration specimens among the same cohort of patients whose survival outcomes have been reported. RESULTS: Twenty patients had specimens available. Nineteen globes revealed no abnormalities of the iris, ciliary body, lens, retinal pigment epithelium, choroid, or chorioretinal vasculature. Eighteen globes showed no optic nerve abnormalities. One globe from a patient who refused exenteration until adenoid cystic carcinoma recurrence supervened demonstrated optic nerve edema with a peripapillary hemorrhage and cotton wool spot, as well as hemorrhage and necrosis within an extraocular muscle. Eighteen globes showed no retinal abnormalities attributable to intra-arterial chemotherapy. Three globes showed incidental retinal findings: 2 globes contained 1 to 2 small peripheral retinal hemorrhages and 1 had a pigmented retinal hole. Seven demonstrated mild, chronic extraocular muscle inflammation, and 13 had unremarkable musculature. The single patient who received IACC via the internal carotid rather than the external carotid artery developed ophthalmic artery occlusion with orbital apex syndrome prior to exenteration, and diffuse necrosis and hemorrhage were evident histopathologically. CONCLUSIONS: Neoadjuvant IACC does not cause significant histopathologic damage to key ocular structures or compromise visual function in patients receiving intra-arterial chemotherapy through the external carotid artery. However, delivering chemotherapy through the internal carotid artery may result in visually significant thrombotic vascular events. The generally benign histopathological findings in these exenteration specimens support the concept of IACC delivery through the external carotid system as the cornerstone of a future globe-preserving strategy for lacrimal gland adenoid cystic carcinoma.

Orbital Bony Reconstruction With Presized and Precontoured Porous Polyethylene-Titanium Implants.

PURPOSE: Complex bony orbital defects are reconstructively challenging due to loss of intraoperative anatomical landmarks and adjacent support. Presized and precontoured porous polyethylene-titanium implants (Medpor Titan 3D Orbital Floor Implant) are designed to reestablish normal orbital floor and medial wall anatomy and are modeled after anatomically averaged orbits. This is the first study to report clinical outcomes with this implant. METHODS: This retrospective case series reviewed clinical data and outcomes for patients undergoing orbital reconstruction with a presized and precontoured porous polyethylene-titanium orbital implant from January 2016 to June 2018. RESULTS: A total of 34 orbits of 33 patients were identified (mean age: 43 ± 16 years, 70% men). Most bony defects were a result of trauma and included large orbital floor deformities (100%), medial wall defects (74%), disrupted inferomedial struts (68%), and broken posterior ledges (82%). Symptomatic diplopia (73%) and enophthalmos (89%, mean: 3.7 ± 2.1 mm) were common preoperatively. Many cases were revisions (44%). Mean follow up was 7.8 ± 6.7 months. All patients had improved globe positioning, enophthalmos, and hypoglobus. Seven patients had persistent postoperative diplopia: 6 responded to prism therapy and 1 required strabismus surgery. One patient required retrobulbar hematoma drainage and 1 patient required implant explantation due to chronic infection. CONCLUSIONS: Commercially available presized and precon toured porous polyethylene-titanium implants are useful for complex orbital bony defects and can achieve functional improve ments in diplopia, enophthalmos, and extraocular motility with a low incidence of postoperative complications or revisional surgery.

mRNA decapping factors and the exonuclease Xrn2 function in widespread premature termination of RNA polymerase II transcription.

We report a function of human mRNA decapping factors in control of transcription by RNA polymerase II. Decapping proteins Edc3, Dcp1a, and Dcp2 and the termination factor TTF2 coimmunoprecipitate with Xrn2, the nuclear 5'-3' exonuclease "torpedo" that facilitates transcription termination at the 3' ends of genes. Dcp1a, Xrn2, and TTF2 localize near transcription start sites (TSSs) by ChIP-seq. At genes with 5' peaks of paused pol II, knockdown of decapping or termination factors Xrn2 and TTF2 shifted polymerase away from the TSS toward upstream and downstream distal positions. This redistribution of pol II is similar in magnitude to that caused by depletion of the elongation factor Spt5. We propose that coupled decapping of nascent transcripts and premature termination by the "torpedo" mechanism is a widespread mechanism that limits bidirectional pol II elongation. Regulated cotranscriptional decapping near promoter-proximal pause sites followed by premature termination could control productive pol II elongation.

The Flip-Back Myocutaneous Advancement Flap for Periocular Reconstruction.

PURPOSE: To present a novel myocutaneous flap for anterior lamellar reconstruction. METHODS: Retrospective interventional case series of consecutive patients who underwent Mohs reconstruction using the flip-back flap. Operations were performed by a single surgeon (DTT) between January 2012 and May 2016. For lower eyelid defects, an extended subciliary incision was made and a skin-muscle flap developed and suspended in the manner of lower eyelid blepharoplasty. A back-cut was used to develop a pedicle from the overlapping tissue, which was then rotated 180 degrees into the defect. A similar method was employed in an inverted manner for upper eyelid defects. Postoperative eyelid function, cosmesis, complications, and need for further interventions were assessed. RESULTS: Ten patients-8 with lower and 2 with upper eyelid defects-were reconstructed using this method. Mean follow up was 18.3 ± 15.5 months with a minimum interval of 4 months. Despite the 180-degree rotation of a relatively narrow pedicle, none of the patients experienced flap necrosis. Postoperative function and cosmesis was satisfactory, with no tissue puckering, notching, or symptomatic retraction. No antimetabolite/steroid injection or surgical revision was required. CONCLUSIONS: The flip-back flap expands the armamentarium of the periocular reconstructive surgeon. Its particular forte is in addressing broad and relatively shallow anterior lamellar defects where sufficient tissues are not available for transposition via a uni- or bipedicle flap. By leveraging the robust periocular vascular plexus and defying traditional guidelines governing pedicle formation and rotation, it permits creation of a local flap in cases where skin grafts or extensive Mustarde-style flaps might otherwise be required.The flip-back myocutaneous flap offers a novel alternative to skin grafting or more extensive cheek rotational flaps for reconstruction of challenging anterior lamellar defects involving the eyelids and adjacent periocular tissues.

Ocular and cerebral infarction from periocular filler injection.

A 20-year-old woman presented with loss of vision in her right eye and a "black nose" after receiving hyaluronic acid filler injections in her right glabella 1 month prior. Her vision was no light perception, and external examination revealed resolving skin necrosis at the nasal tip. A dilated fundus exam showed a fibrotic membrane emanating from a pale optic nerve and a diffusely atrophic retina with sclerotic vessels. An MRI demonstrated scattered right-sided parietal lobe infarcts. These findings were consistent with inadvertent cannulation of the supraorbital artery, followed by injection of filler into the internal carotid circulation. The product traveled in a retrograde fashion, occluding the right ophthalmic artery, right dorsal nasal artery, and arterial segments to the Circle of Willis. This case highlights the importance of understanding the complex vascular architecture of the periorbita and the mechanism by which such occlusions occur.

Dog bite injuries of the eye and ocular adnexa.

Dog bites result in a diverse range of injuries and complications in the periocular region, particularly in school aged children. It is therefore incumbent on the oculoplastic surgeon to be well versed in both acute and long-term management. The intent of this review is to provide a systematic evaluation of the epidemiology, principles of dog bite wound care, and specific considerations related to common patterns of ophthalmic injury. Review of clinical literature from 1976 to 2014. The majority of periocular injuries result from seemingly benign interactions between young children and familiar dogs. Aggressive saline lavage combined with selective debridement of devitalized tissue is essential. High-risk wounds and vulnerable patient groups may benefit from preventive antibiotic coverage as well as appropriate rabies and tetanus prophylaxis. While the nuances of surgical repair are variable given the heterogeneity of presentation, systematic examination and an algorithm-driven approach underlie the optimal management of these complex injuries.

Ablative Fractional Laser Resurfacing With Laser-Assisted Delivery of 5-Fluorouracil for the Treatment of Cicatricial Ectropion and Periocular Scarring.

PURPOSE: Cicatricial ectropion and periocular scarring can cause significant functional and cosmetic deficits. Surgical treatments can be associated with recicatrization, donor site morbidity, and textural and pigmentary abnormalities. This case series reports on efficacy and safety of a novel nonsurgical approach to treating cicatricial ectropion using ablative fractional laser resurfacing and laser-assisted delivery of 5-fluorouracil. METHODS: A retrospective review was conducted of all patients at a single institution who received ≥3 rounds of ablative fractional laser resurfacing with laser-assisted delivery of 5-fluorouracil. Six patients with cicatricial ectropion and periocular scarring secondary to reconstructive surgery, traumatic lacerations, and facial burns were included. Aesthetic and functional improvement were evaluated via fluorescein staining, tear breakup time, external photography, questionnaires gauging dry eye symptoms, and scar appearance. RESULTS: All patients showed functional improvement based on fluorescein staining (mean improvement 6.0 ± 1.4; p = 0.0007) and other indicators of dry eye. All 4 patients with lagophthalmos improved and 2 showed complete resolution. All patients demonstrated significant cosmetic improvement based on a validated scar assessment questionnaire (mean improvement 37.5 ± 18.9; p = 0.004), and 5 of 6 patients reported improved satisfaction with scar appearance (mean improvement 19.3 ± 12.8; p = 0.014). There were no adverse effects reported. CONCLUSIONS: Ablative fractional laser resurfacing with laser-assisted delivery of 5-fluorouracil appears to be a safe and effective modality for treating the functional and aesthetic abnormalities associated with periocular scarring, yielding results that are difficult to attain through surgery alone. Optimal management of cicatricial ectropion and periocular scarring often requires multimodality treatment, and ablative fractional laser resurfacing with laser-assisted delivery of 5-fluorouracil may be considered as part of a comprehensive approach to managing periocular scars.

Bioengineered dermal substitutes for the management of traumatic periocular tissue loss.

PURPOSE: Traumatic periocular injuries occasionally result in significant soft tissue loss, for which there are limited management options that provide satisfactory cosmetic and functional outcomes. The authors describe the use of a bioengineered dermal substitute (Integra® Dermal Regeneration Template [DRT], Integra LifeSciences, Plainsboro, NJ) as an alternative to immediate flap reconstruction or skin grafting. METHODS: Retrospective interventional case series of patients who underwent DRT placement for periocular tissue loss at the time of trauma. In each case, primary closure or immediate flap reconstruction was deemed impractical or undesirable due to the size and location of the primary and associated secondary defects. One to four weeks later, the outer silicone layer was removed and healing assessed. Additional reconstructive techniques were performed as needed. RESULTS: Three patients were treated at Bascom Palmer Eye Institute and one at Byers Eye Institute at Stanford. The defects healed completely in two patients, and by 79.2% in a third, with no need for additional reconstructive surgery. In the remaining patient, the defect was significantly downsized by 56.1%, allowing for a simpler flap reconstruction. CONCLUSIONS: Bioengineered dermal substitutes should be considered as a viable alternative to traditional reconstructive techniques for large periocular defects resulting from trauma. The outer silicone layer prevents desiccation and serves as a protective barrier, while the inner collagen matrix organizes the growth of neo-dermis and minimizes wound contraction. The dimensions of cutaneous defects can therefore be reduced dramatically, potentially eliminating the need for skin grafting and/or reducing the ultimate complexity of flap reconstruction.

Gene promoters dictate histone occupancy within genes.

Spt6 is a transcriptional elongation factor and histone chaperone that reassembles transcribed chromatin. Genome-wide H3 mapping showed that Spt6 preferentially maintains nucleosomes within the first 500 bases of genes and helps define nucleosome-depleted regions in 5' and 3' flanking sequences. In Spt6-depleted cells, H3 loss at 5' ends correlates with reduced pol II density suggesting enhanced transcription elongation. Consistent with its 'Suppressor of Ty' (Spt) phenotype, Spt6 inactivation caused localized H3 eviction over 1-2 nucleosomes at 5' ends of Ty elements. H3 displacement differed between genes driven by promoters with 'open'/DPN and 'closed'/OPN chromatin conformations with similar pol II densities. More eviction occurred on genes with 'closed' promoters, associated with 'noisy' transcription. Moreover, swapping of 'open' and 'closed' promoters showed that they can specify distinct downstream patterns of histone eviction/deposition. These observations suggest a novel function for promoters in dictating histone dynamics within genes possibly through effects on transcriptional bursting or elongation rate.

Split face evaluation of long-pulsed non-ablative 1,064 nm Nd:YAG laser for treatment of direct browplasty scars.

PURPOSE: To investigate 1,064 nm long-pulse Nd:YAG laser for postoperative treatment of direct browplasty scars. METHODS: Nine patients who underwent direct browplasty were enrolled in this prospective study. Subjects were randomized to unilateral laser treatment at 2-week intervals for six total treatments, with the contralateral scar used as a control. Prior to each treatment, subjects rated treated and control scars on overall cosmesis. Post-treatment, subjects rated each for erythema, swelling, discomfort, and perceived hair loss. Finally, examiners masked to treatment side were asked to judge side-by-side photographs of first and final visits for improvement and side effects. RESULTS: Subjects rated the overall appearance of the treated scar significantly higher at the time of treatment number 5 (mean score 5.13 ± 2.03, P = 0.008) and treatment number 6 (6.25 ± 1.98, P = 0.005) compared to treatment 1 (3.75 ± 2.12); by contrast, they failed to rate the control scar more highly. On masked examination of photographs, the treated scar was selected as most improved 50.0 ± 12.5% of the time. Both subjects and graders reported side effects as transient and mild to moderate (mean score 1-4), with no reports of hair loss from either subjects or observers. CONCLUSIONS: The 1,064 nm Nd:YAG laser provided significant improvement in scar cosmesis after direct browplasty, as rated by subject self-report, but not by masked observers, and appears to be a useful tool for increasing satisfaction among those dissatisfied with direct browplasty scars. Side effects-including erythema, edema, and discomfort-were transient and universally rated as mild to moderate. Lasers Surg. Med. 48:742-747, 2016. © 2016 Wiley Periodicals, Inc.

Novel Pigtail Cannula for a Canalicular-Involving Eyelid Laceration.

An 89-year-old woman presented with a canalicular-involving laceration/avulsion of the right lower eyelid after a fall. The inferior canaliculus was severed deep within the wound, and the ends were difficult to identify. Novel pigtail cannulas, designed by the authors, were used for lacrimal system intubation and suture passage. Satisfactory cosmetic and functional results were achieved. These cannulas facilitate repair by integrating multiple functionalities in a single instrument. Once a cannula has been inserted and rotated, the location of fluid egress provides important clues. If injected saline appears in the nasopharynx but not in the wound, absence of a common canaliculus can be suspected. Injection of viscoelastic, air or fluorescein-impregnated saline also permits easier identification of the cut end of the canaliculus within the wound and facilitates appropriate rotation of the pigtail.

Idiopathic Unilateral Enlargement of the Extraocular Muscles in an Infant.

A 6-month-old boy presented with a unilateral motility deficit of the right eye in all fields of gaze. Neuroimaging revealed unilateral enlargement of the medial, lateral, and inferior rectus muscles with sparing of the tendons. An evaluation for thyroid eye disease, idiopathic orbital inflammation, myositis, inflammatory and neoplastic infiltration of the muscle, vascular anomalies, and metastatic neuroblastoma was unrevealing. Biopsy of the muscle revealed normal architecture with an absence of inflammation, infiltration, or fibrosis. A review of the literature reveals the exceptionally rare nature of this finding. While the authors cannot rule out an atypical case of congenital euthyroid eye disease, this constellation of findings is not consistent with thyroid eye disease and may represent previously described cases of idiopathic enlargement of the extraocular muscles.

The Locking Y Lateral Canthopexy With Osseous Integration: Clinical Experience and Surgical Technique.

PURPOSE: To describe a surgical technique to correct lateral canthal tendon disinsertion with a strabismus surgery-inspired locking capture of the tendon complex and osseous integration via drill holes. METHODS: Retrospective interventional case series including all patients with lateral canthal tendon disinsertion who underwent locking Y lateral canthopexy with drill hole reinforcement by 1 surgeon (D.T.T.) between 2006 and 2011. Outcome measures included resolution of presenting ocular symptoms, improved blink dynamics and lid closure, correction of lagophthalmos and exposure keratopathy, and need for further surgery. RESULTS: A total of 53 lateral canthopexies with osseous integration were performed in 42 patients who fulfilled clinical criteria for lateral canthal tendon disinsertion. The population was biased toward treatment failures; 81% of eyes (43/53) had a history of prior lateral canthal tightening, and of these 30.2% (16/53) had undergone 3 or more procedures. Postoperatively, all eyes demonstrated improved eyelid position and blink mechanics, and 83% (44/53) had subjective resolution of epiphora and ocular irritation. Lagophthalmos was fully corrected in 95% (19/20) of cases, and corneal staining resolved in 88% (14/16). With a mean follow-up period of 24 months, 3.7% of eyes (2/53) required additional lateral canthal tightening. CONCLUSIONS: The locking Y lateral canthopexy is an effective and durable method for repositioning the lateral canthal tendon complex to improve blink dynamics, eyelid closure, and cosmesis. Even in a population heavily biased toward treatment failure, clinical results are excellent and the reoperation rate is low.