January 2019

OBJECTIVE: Corneal nerve damage may result in neuropathic corneal pain (NCP). Autologous serum tears (AST) have been shown to results in nerve regeneration and may help alleviate corneal pain. This study aimed to evaluate the efficacy of AST in the treatment of NCP. METHODS: This was a retrospective case-control study. Sixteen patients suffering from severe NCP and no current ocular surface disease were compared to 12 controls. In vivo confocal microscopy (IVCM) (HRT3/RCM; Heidelberg, Germany) of the central corneas was performed bilaterally. Change in pain severity (scale of 0-10), corneal nerve density, tortuosity, reflectivity and presence of beading and microneuromas before and after treatment were recorded. RESULTS: All patients had severe pain of 9.1 ± 0.2 (range 8-10). Before treatment, subbasal nerves were significantly decreased compared to controls, including total nerve length (10,935.5 ± 1264.3 vs. 24,714.4 ± 1056.2 μm/mm; p < 0.0001) and total number of nerves (10.5 ± 1.4 vs. 28.6 ± 2.0; p < 0.0001), respectively. Morphologically, significantly increased reflectivity (2.9 ± 0.2 vs. 1.2 ± 0.1; p = 0.00008) and tortuosity (2.4 ± 0.2 vs. 1.7 ± 0.1; p = 0.001), both graded on a scale of 0-4, were noted. After 3.8 ± 0.5 months (range 1-8 months) of AST treatment, pain severity decreased to 3.1 ± 0.3 (range 0-4), (p < 0.0001). Further, IVCM demonstrated a significant improvement (p < 0.005) in total nerve length (17,351.3 ± 1395.6 μm/mm) and number (15.1 ± 1.6) as well as significant decrease in reflectivity (2.4 ± 0.2; p = 0.001) and tortuosity (2.2 ± 0.2; p = 0.001). CONCLUSION: IVCM demonstrates underlying alterations of the subbasal corneal nerve plexus in patients suffering from debilitating NCP. AST-induced nerve regeneration is seen following treatment with AST, which correlates with improvement in patient symptoms of NCP.

Lipopeptide daptomycin is a last-line cell-membrane-targeting antibiotic to treat multidrug-resistant Alarmingly, daptomycin-resistant isolates have emerged. The mechanisms underlying daptomycin resistance are diverse and share similarities with resistances to cationic antimicrobial peptides and other lipopeptides, but they remain to be fully elucidated. We selected mutants with increased resistance to daptomycin from a library of transposon insertions in sequent type 8 (ST8) HG003. Insertions conferring increased daptomycin resistance were localized to two genes, one coding for a hypothetical lipoprotein (SAOUHSC_00362, Dsp1), and the other for an alkaline shock protein (SAOUHSC_02441, Asp23). Markerless loss-of-function mutants were then generated for comparison. All transposon mutants and knockout strains exhibited increased daptomycin resistance compared to those of wild-type and complemented strains. Null and transposon insertion mutants also exhibited increased resistance to cationic antimicrobial peptides. Interestingly, the mutant also showed increased resistance to vancomycin, a cell-wall-targeting drug with a different mode of action. Null mutations in both and resulted in increased tolerance as reflected by reduced killing to both daptomycin and vancomycin, as well as an increased tolerance to surfactant (Triton X-100). Neither mutant exhibited increased resistance to lysostaphin, a cell-wall-targeting endopeptidase. These findings identified two genes core to the species that make previously uncharacterized contributions to antimicrobial resistance and tolerance in .

OBJECTIVES: To evaluate the impact of a comprehensive cataract surgery curriculum on the incidence of intraoperative complications. DESIGN: We retrospectively compared the total number of cataract surgeries that the residents performed in all of the teaching sites, and the incidences of intraoperative complications (anterior capsule tear, posterior capsule rent, vitreous loss, anterior vitrectomy, zonular dialysis, iris trauma, hemorrhage, dropped lens fragment, corneal wound burn, incorrect intraocular lens) for the surgeries performed at Massachusetts Eye & Ear by residents in the pre-intervention group (residents graduating in 2004 and 2005), before the implementation of a surgical curriculum, and the residents in the post-intervention group (residents graduating in 2014 and 2015). SETTING: Ophthalmology residency program at a major academic institution. PARTICIPANTS: Residents graduating in 2004, 2005, 2014, and 2015. RESULTS: We reviewed 4373 charts. 2086 of those surgeries were performed at Massachusetts Eye & Ear. The incidence of posterior capsule rent/vitreous loss/anterior vitrectomy was lower in the post-intervention group (1.4% versus 7.7%, p < 0.0001). Other complications were also lower in the post-intervention group. CONCLUSIONS: Implementation of a comprehensive cataract surgery curriculum focusing on pre-operative, intra-operative and post-operative interventions, with an emphasis on patient outcomes resulted in a decrease in the rate of intraoperative complications.

Importance: Identifying the factors that are associated with the magnitude of treatment benefits from anti-vascular endothelial growth factor (anti-VEGF) therapy for diabetic macular edema (DME) may help refine treatment expectations. Objective: To identify the baseline factors that are associated with vision and anatomic outcomes when managing DME with anti-VEGF and determine if there are interactions between factors and the agent administered. Design, Setting, and Participants: This post hoc analysis of data from the Diabetic Retinopathy Clinical Research Network multicenter randomized clinical trial , Protocol T, was conducted between December 2016 and December 2017. Between August 22, 2012, and August 28, 2013, 660 participants were enrolled with central-involved DME and vision impairment (approximate Snellen equivalent, 20/32-20/320). Interventions: Repeated 0.05-mL intravitreous injections of 2.0-mg aflibercept (201 eyes), 1.25-mg bevacizumab (185 eyes), or 0.3-mg ranibizumab (192 eyes) per protocol. Main Outcomes and Measures: Change in visual acuity (VA) and optical coherence tomography (OCT) central subfield thickness at 2 years and change in VA over 2 years (area under the curve [AUC]). Results: Among 578 participants, the median age (interquartile range) was 61 (54-67) years. Across anti-VEGF treatment groups, each baseline factor was associated with mean improvement in VA and a reduction in central DME compared with the baseline. For every decade of participant age, the mean VA improvement was reduced by 2.1 letters (95% CI, -3.0 to -1.2; P < .001) in the VA and 1.9 letters (95% CI, -2.4 to -1.3; P < .001) in the VA AUC analyses. For each 1% increase in hemoglobin A1c levels, VA improvement was reduced by 1 letter in the VA (95% CI, -1.5 to -0.5; P < .001) and 0.5 letters (95% CI, -0.9 to -0.2; P < .001) in the VA AUC analyses. Eyes with no prior panretinal photocoagulation (PRP) and less than severe nonproliferative diabetic retinopathy had an approximately 3-letter improvement in the VA (95% CI, 0.9-5.4; P = .007) and VA AUC (95% CI, 1.3-4.2; P < .001) analyses compared with eyes with prior PRP. On average, African American participants had greater reductions in central subfield thickness compared with eyes of white participants (-27.3 μm, P = .01), as did eyes with central subretinal fluid compared with eyes without this OCT feature (-22.9 μm, P = .01). There were no interactions between the predictive factors and the specific anti-VEGF agent that was administered for any VA or OCT outcome. Conclusions and Relevance: Lower hemoglobin A1c levels were associated with the magnitude of vision improvement following anti-VEGF therapy, providing further evidence to encourage glycemic control among persons with diabetes. Younger patients and those without prior PRP might expect greater improvement in VA than older patients or those with prior PRP.

Optic neuropathy is one of the leading causes of irreversible blindness caused by retinal ganglion cell (RGC) degeneration. The development of induced pluripotent stem cell (iPSC)-based therapy opens a therapeutic window for RGC degeneration, and tissue engineering may further promote the efficiency of differentiation process of iPSCs. The present study was designed to evaluate the effects of a novel biomimetic polybenzyl glutamate (PBG) scaffold on culturing iPSC-derived RGC progenitors. The iPSC-derived neural spheres cultured on PBG scaffold increased the differentiated retinal neurons and promoted the neurite outgrowth in the RGC progenitor layer. Additionally, iPSCs cultured on PBG scaffold formed the organoid-like structures compared to that of iPSCs cultured on cover glass within the same culture period. With RNA-seq, we found that cells of the PBG group were differentiated toward retinal lineage and may be related to the glutamate signaling pathway. Further ontological analysis and the gene network analysis showed that the differentially expressed genes between cells of the PBG group and the control group were mainly associated with neuronal differentiation, neuronal maturation, and more specifically, retinal differentiation and maturation. The novel electrospinning PBG scaffold is beneficial for culturing iPSC-derived RGC progenitors as well as retinal organoids. Cells cultured on PBG scaffold differentiate effectively and shorten the process of RGC differentiation compared to that of cells cultured on coverslip. The new culture system may be helpful in future disease modeling, pharmacological screening, autologous transplantation, as well as narrowing the gap to clinical application.

Immunotherapy is a developing but very promising arsenal to treat cancer. Acquiring a more potent and effective approach in cancer immunotherapy is always the ultimate pursuance. CTL-based therapies are highly acclaimed recently due to its direct killing property. However, difficulty in obtaining adequate number of CTLs is still a major obstacle. In previous studies, it is shown that pluripotent stem cell-derived cytotoxic T lymphocytes (CTL)-especially the genetically engineered tumor antigen-specific CTLs-may serve as a good candidate for this goal. Here we introduce a novel approach in generating tumor antigen-specific CTLs from induced pluripotent stem cells (iPSCs) by using both in vitro and in vivo priming mechanisms for the tumor management in a murine melanoma model.

Purpose: People with central vision loss (CVL) often report difficulties watching video. We objectively evaluated the ability to follow the story (using the information acquisition method). Methods: Subjects with CVL (n = 23) or normal vision (NV, n = 60) described the content of 30-second video clips from movies and documentaries. We derived an objective information acquisition (IA) score for each response using natural-language processing. To test whether the impact of CVL was simply due to reduced resolution, another group of NV subjects (n = 15) described video clips with defocus blur that reduced visual acuity to 20/50 to 20/800. Mixed models included random effects correcting for differences between subjects and between the clips, with age, gender, cognitive status, and education as covariates. Results: Compared to both NV groups, IA scores were worse for the CVL group (P < 0.001). IA reduced with worsening visual acuity (P < 0.001), and the reduction with worsening visual acuity was greater for the CVL group than the NV-defocus group (P = 0.01), which was seen as a greater discrepancy at worse levels of visual acuity. Conclusions: The IA method was able to detect difficulties in following the story experienced by people with CVL. Defocus blur failed to recreate the CVL experience. IA is likely to be useful for evaluations of the effects of vision rehabilitation.

Commonly, saccades are thought to be ballistic eye movements, not modified during flight, with a straight path and a well-described velocity profile. However, they do not always follow a straight path and studies of saccade curvature have been reported previously. In a prior study, we developed a real-time, saccade-trajectory prediction algorithm to improve the updating of gaze-contingent displays and found that saccades with a curved path or that deviated from the expected velocity profile were not well fit by our saccade-prediction algorithm (velocity-profile deviation), and thus had larger updating errors than saccades that had a straight path and had a velocity profile that was fit well by the model. Further, we noticed that the curved saccades and saccades with high velocity-profile deviations were more common than we had expected when participants performed a natural-viewing task. Since those saccades caused larger display updating errors, we sought a better understanding of them. Here we examine factors that could affect curvature and velocity profile of saccades using a pool of 218,744 saccades from 71 participants watching "Hollywood" video clips. Those factors included characteristics of the participants (e.g., age), of the videos (importance of faces for following the story, genre), of the saccade (e.g., magnitude, direction), time during the session (e.g., fatigue) and presence and timing of scene cuts. While viewing the video clips, saccades were most likely horizontal or vertical over oblique. Measured curvature and velocity-profile deviation had continuous, skewed frequency distributions. We used mixed-effects regression models that included cubic terms and found a complex relationship between curvature, velocity-profile deviation and saccade duration (or magnitude). Curvature and velocity-profile deviation were related to some video-dependent features such as lighting, face presence, or nature and human figure content. Time during the session was a predictor for velocity profile deviations. Further, we found a relationship for saccades that were in flight at the time of a scene cut to have higher velocity-profile deviations and lower curvature in univariable models. Saccades characteristics vary with a variety of factors, which suggests complex interactions between oculomotor control and scene content that could be explored further.

Enterococcus faecalis are a major cause of nosocomial infection worldwide, and the spread of vancomycin resistant strains (VRE) limits treatment options. Tigecycline-resistant VRE began to be isolated from inpatients at a Brazilian hospital within months following the addition of tigecycline to the hospital formulary. This was found to be the result of a spread of an ST103 E. faecalis clone. Our objective was to identify the basis for tigecycline resistance in this lineage. The genomes of two closely related tigecycline-susceptible (MIC = 0.06 mg/L), and three representative tigecycline-resistant (MIC = 1 mg/L) ST103 isolates were sequenced and compared. Further, efforts were undertaken to recapitulate the emergence of resistant strains in vitro. The specific mutations identified in clinical isolates in several cases were within the same genes identified in laboratory-evolved strains. The contribution of various polymorphisms to the resistance phenotype was assessed by trans-complementation of the wild type or mutant alleles, by testing for differences in mRNA abundance, and/or by examining the phenotype of transposon insertion mutants. Among tigecycline-resistant clinical isolates, five genes contained non-synonymous mutations, including two genes known to be related to enterococcal tigecycline resistance (tetM and rpsJ). Finally, within the in vitro-selected resistant variants, mutation in the gene for a MarR-family response regulator was associated with tigecycline resistance. This study shows that E. faecalis mutates to attain tigecycline resistance through the complex interplay of multiple mechanisms, along multiple evolutionary trajectories.

The original version of this Article contained errors in the spelling of the authors Fan Liu and M. Arfan Ikram, which were incorrectly given as Fan Lui and Arfan M. Ikram. In addition, the original version of this Article also contained errors in the author affiliations which are detailed in the associated Publisher Correction.

Angiogenesis, disruption of the retinal barrier, leukocyte-adhesion and oedema are cardinal signs of proliferative retinopathies that are associated with vision loss. Therefore, identifying factors that regulate these vascular dysfunctions is critical to target pathological angiogenesis. Given the conflicting role of bioactive lipids reported in the current literature, the goal of this review is to provide the reader a clear road map of what has been accomplished so far in the field with specific focus on the role of polyunsaturated fatty acids (PUFAs)-derived metabolites in proliferative retinopathies. This necessarily entails a description of the different retina cells, blood retina barriers and the role of (PUFAs)-derived metabolites in diabetic retinopathy, retinopathy of prematurity and age-related macular degeneration as the most common types of proliferative retinopathies.

AIM: To systematically review whether the increased fluctuation of intraocular pressure (IOP) is a risk factor for open angle glaucoma (OAG) progression. METHODS: Scientific studies relevant to IOP fluctuation and glaucoma progression were retrieved from MEDLINE, EMBASE and CENTRAL databases, and were listed as references in this paper. The hazard ratio (HR) was calculated by using fixed or random-effects models according to the heterogeneity of included studies. RESULTS: Individual data for 2211 eyes of 2637 OAG patients in fourteen prospective studies were included in this Meta-analysis. All studies were longitudinal clinical studies with follow-up period ranging from 3 to 8.5y. The combined HR was 1.23 (95%CI 1.04-1.46, =0.02) for the association between IOP fluctuation and glaucoma onset or progression with the evidence of heterogeneity (<0.1). Subgroup analyses with different types of IOP fluctuation were also evaluated. Results indicated that the summary HR was 0.98 (95%CI 0.78-1.24) in short-term IOP fluctuation group, which showed no statistical significance with heterogeneity, whereas, the combined HR was 1.43 (95%CI 1.13-1.82, =0.003) in long-term IOP fluctuation group without homogeneity. Sensitivity analysis further showed that the pooled HR was 1.10 (95%CI 1.03-1.18, =0.004) for long-term IOP fluctuation and visual function progression with homogeneity among studies (=0.3). CONCLUSION: Long-term IOP fluctuation can be a risk factor for glaucoma progression based on the presented evidence. Thus, controlling the swing of IOP is crucial for glaucoma or glaucoma suspecting patients.

PURPOSE: Introduction of a novel sensory grading system to assess the incidence and long-term recovery of infraorbital hypesthesia following orbital floor and inferior orbital rim fractures. METHODS: Patients who presented for evaluation of orbital floor and/or zygomaticomaxillary complex (ZMC) fractures between January 2015 and April 2016 were analyzed. Two-point subjective infraorbital sensory grading in 5 discrete anatomic areas was performed. Fractures were repaired based on traditional criteria; hypesthesia was not an indication for surgery. The sensory grading system was repeated a mean 21.7 months (range 18-28) after initial fracture. RESULTS: Sixty-two patients (mean 41.8 years) participated in the initial symptom grading, and 42 patients (67.7%) completed the 2-year follow-up. Overall, 20 of 42 patients (47.6%) had some infraorbital hypesthesia. There were fewer with isolated orbital floor fractures versus ZMC fractures (31.8% vs. 68.4%; p = 0.019). Two years postinjury, 9.1% and 40.0% with isolated floor and ZMC fractures, respectively, had persistent sensory disturbance (p = 0.0188). Of patients with sensory disturbance on presentation, 71.4% with isolated floor fractures and 38.5% with ZMC fractures experienced complete sensory recovery (p = 0.1596). Patients with isolated floor fractures had improved recovery after surgery (100% vs. 33.3% recovery; p = 0.0410). Patients with ZMC fractures showed no difference in sensory prognosis between those repaired and observed. CONCLUSIONS: In this pilot study, isolated orbital floor fractures carried a good infraorbital sensory prognosis, further improved by surgical repair. Zygomaticomaxillary complex fractures portended a worse long-term sensory outcome, unaffected by management strategy. This study validates the novel sensory grading system in post-fracture analysis.

PURPOSE OF REVIEW: Continuous curvilinear manual capsulorhexis is currently the standard of cataract surgery. In the past several years, new technologies have been developed to improve the consistency and safety of capsulorhexis creation. This article reviews the most recent technologies in capsulotomy formation and their advantages and disadvantages. RECENT FINDINGS: Guidance devices, femtosecond laser capsulotomy and precision pulse capsulotomy improve the centration, circularity and precision of anterior capsulorhexis and capsulotomy. These developments show particular promise for complex cataract surgeries, though clinical data on the refractive outcomes and complication rates of these technologies are currently limited and warrant additional investigation. SUMMARY: New technological advances in capsulorhexis help surgeons achieve a more ideal capsulotomy geometry. Whether this translates into more predictable refractive outcomes and safer surgeries remains an area of future study.

PURPOSE: To review the published literature assessing the efficacy of β-blockers for the treatment of periocular hemangioma in infants. METHODS: Literature searches were conducted in May 2018 in PubMed with no date restrictions and limited to studies published in English and in the Cochrane Library database without any restrictions. The combined searches yielded 437 citations. Of these,16 articles were deemed appropriate for inclusion in this assessment and assigned a level of evidence rating by the panel methodologist. RESULTS: None of the 16 studies included in this assessment were rated level I, 3 were rated level II, and 13 were rated level III. The most common treatment regimen was 2 mg/kg daily oral propranolol, but intralesional and topical β-blockers were also used. Treatment effect was most often measured in terms of reduction in the size of the lesions, which occurred in the majority of patients. β-Blockers were consistently shown to reduce astigmatism, but this reduction was shown to be statistically significant in only 2 series. The effect of β-blockers on amblyopia was not adequately documented. β-Blockers were generally well tolerated and had mild side effects (fatigue, gastrointestinal upset/diarrhea, restlessness/sleep disturbances, minor wheezing, and cold extremities). Complications severe enough to require cessation of treatment occurred in only 2 patients out of a total of 229 who received β-blockers. CONCLUSIONS: There is limited evidence to support the safety and efficacy of both topical and systemic β-blockers to promote regression of periocular hemangiomas. Additional research may confirm the best dosage and route of administration to maximize efficacy in reducing induced astigmatism and amblyopia associated with periocular hemangiomas while minimizing side effects.

Emmanuelle Souzeau, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this Article. This has now been corrected in both the PDF and HTML versions of the Article.

An 87-year-old woman not known to have either a lymphoma or leukemia developed a left multinodular, fish-flesh superior epibulbar and forniceal mass. A biopsy disclosed a blastic tumor with scattered multinucleated immature megakaryoblasts. Immunophenotyping of bone marrow cells revealed strong positivity for CD7, CD31, CD43, CD45, CD61, and CD117; CD71, myeloperoxidase, and lysozyme were also positive in scattered cells. Forty percent of the neoplastic cells were Ki-67 positive. Cytogenetic studies indicated a trisomy 8 (associated with worse prognosis) and a t(12; 17) translocation. Desmin, smooth muscle actin, pancytokeratin, CAM 5.2, adipophilin, tryptase, S100, SOX10, MART1, and E-cadherin were negative, ruling out a nonhematopoietic tumor. The conjunctival lesion was diagnosed as a myeloid sarcoma with megakaryoblastic differentiation, a rare variant. It probably arose from a myelodysplastic syndrome. This is the first case of its type to develop in the conjunctiva.

PURPOSE: To assess the hypothesis that fluorometholone 0.1% eye drops are safe and effective as adjunctive therapy for trachomatous trichiasis (TT) surgery; determining the most promising dose. DESIGN: Randomized, placebo-controlled, double-masked parallel dose-ranging clinical trial. METHODS: Patients undergoing upper lid TT surgery at a rural Ethiopian hospital were randomized to fluorometholone 0.1% twice daily for 4 weeks, 4 times daily for 4 weeks, 4 times daily for 8 weeks, or matching frequency placebo in a 3:1:3:1:3:1 ratio for 1 eye. Randomization was stratified by TT severity (1-4 vs ≥5 lashes touching the globe). Safety outcomes (intraocular pressure [IOP] elevation, cataract, and other dose-limiting toxicities) and postoperative TT incidence were assessed over 1 year. RESULTS: Subjects randomized were 39:13:39:13:38:13 in the respective groups, and 1 subject in the 8-weeks fluorometholone group was withdrawn. Of 154 subjects, 148 (96.1%) completed 1 year's follow-up. Among 76 eyes receiving fluorometholone 4 times daily, 1 developed IOP elevation ≥ 30 mm Hg (to 37 mm Hg) and 1 had an allergic reaction attributed to the study drug; each resolved upon drug cessation without sequelae. No cataract or other dose-limiting toxicity events occurred. Postoperative TT within 1 year occurred in 29.3% of placebo eyes vs 17.7%, 19.6%, and 23.2% among the respective fluorometholone groups (P = .29 comparing placebo vs all active treatments combined). CONCLUSIONS: The results suggest fluorometholone 0.1% is likely to be safe and efficacious to reduce postoperative TT following TT surgery, and 1 drop twice daily for 4 weeks is the most promising dose. Confirmation in a full-scale clinical trial is needed before programmatic implementation.

AIMS: To investigate the aetiology and characteristics of dry eye disease (DED) in a Nordic cohort of patients with congenital aniridia. METHODS: Thirty-four Norwegian and one Danish subject with congenital aniridia and 21 healthy controls were examined. All subjects underwent an extensive dry eye examination, including evaluation of meibomian glands (MGs) by meibography, measurement of tear production and tear film osmolarity and grading of vital staining of the ocular surface. Moreover, slit-lamp biomicroscopy was undertaken, including grading of aniridia-associated keratopathy (AAK). RESULTS: Mean tear film osmolarity was significantly higher (314±11 mOsmol/L) in patients with aniridia compared with the healthy control group (303±11 mOsmol/L, p=0.002). Vital staining score was higher in the aniridia group (4.3±3.0) compared with healthy controls (2.4±1.6, p=0.02). The degree of staining correlated positively with the stage of AAK (r=0.44, p=0.008) and negatively with corneal sensitivity (r=-0.45, p=0.012). Number of expressible MGs was lower in aniridia subjects (2.9±1.6) than in controls (4.0±1.3, p=0.007). MG loss, staged from 0 to 3, was higher in the aniridia group than in the control group, both in upper eyelid (0.86±0.89 vs 0.10±0.31, p=0.001) and lower eyelid (0.94±0.73 vs 0.30±0.47, p=0.003). Computerised analyses showed thinning (p=0.004) and lower density (p<0.001) of the MGs compared with the healthy population. CONCLUSIONS: Patients with congenital aniridia demonstrate increased tear film osmolarity, ocular surface staining, loss of MGs and lower MG expressibility. We conclude that meibomian gland dysfunction and keratopathy are related to development of DED in aniridia.

Bell's palsy is the most common neurologic condition affecting the cranial nerves. Lagophthalmos, exposure keratopathy, and corneal ulceration are potential complications. In this review, we evaluate various causes of facial paralysis as well as the level 1 evidence supporting the use of a short course of oral steroids for idiopathic Bell's palsy to improve functional outcomes. Various surgical and nonsurgical techniques are also discussed for the management of residual facial dysfunction.