Durable tumor regression and restoration of neurologic function after treatment with anti-PD-1 in patients with functionally unresectable cutaneous squamous cell carcinoma with perineural spread into the cavernous sinus.

PURPOSE: To describe tumor response and cranial nerve function outcomes after administration of anti-PD-1 to patients with cutaneous squamous cell carcinoma (CSCC) with perineural spread to cranial nerves (CN) extending into the cavernous sinus. METHODS: Electronic patient records from a single institution were queried for patients with CSCC of the head and neck causing diplopia (ICD-10 H53.2) who were treated with anti-PD-1. Data extracted included demographics, duration of anti-PD-1 therapy, immune-mediated adverse reactions, tumor response per adapted RECIST v1.1, and changes in CN function and symptoms (e.g., pain). All patients were prescribed cemiplimab 350 mg IV q3 weeks. RESULTS: Four patients met inclusion criteria. They had varying degrees of pain and sensory deficits in branches of the trigeminal nerve (CN V). One, 2, 3 and 1 patients had baseline involvement of CN III, IV, VI and VII, respectively. MRI confirmed perineural cavernous sinus involvement in all patients. Duration of anti-PD-1 therapy ranged 15-60 weeks. All patients experienced an objective anti-tumor response to anti-PD-1; partial response n = 2, complete response n = 2. At a median follow-up of 22 months, responses were ongoing in all patients. All patients demonstrated improvement in ocular motility deficits and pain with resolution of symptoms in 3 and 1 patients, respectively. CONCLUSION: Administration of anti-PD-1 to patients with CSCC with perineural spread into the cavernous sinus can generate durable anti-tumor regressions and restore CN function, while sparing the morbidity associated with surgical resection and/or radiotherapy. Our findings add to emerging literature supporting this treatment approach for this patient population.

Use of a nasolacrimal stent to treat air regurgitation after dacryocystorhinostomy in a patient using a continuous positive airway pressure device.

The dacryocystorhinostomy procedure creates a direct passageway between the lacrimal sac and nasal cavity, bypassing any nasolacrimal duct obstruction. Use of a continuous positive airway pressure device after dacryocystorhinostomy can cause nasolacrimal air regurgitation. Here, we report a case of air regurgitation after dacryocystorhinostomy that was successfully treated with placement of a Mini Monoka device, a silicone stent used in nasolacrimal surgery to prevent closure of the passageway, in a patient using a continuous positive airway pressure machine. Following the procedure, the patient was able to resume use of her continuous positive airway pressure device. CITATION: Srivatsan S, Mirza M, Imayama I, Setabutr P, Mahoney NR. Use of a nasolacrimal stent to treat air regurgitation after dacryocystorhinostomy in a patient using a continuous positive airway pressure device. J Clin Sleep Med. 2023;19(12):2123-2124.

Severe Mpox Infection of the Eye and Periocular Region.

Mpox is an emerging zoonotic infection with potentially severe ocular and periocular consequences, particularly in immunocompromised patients. This report summarizes 2 cases of fulminant mpox presenting in patients with AIDS. In the first case, confluent lesions resulted in orbital compartment syndrome and total eyelid necrosis. In the second case, eyelid involvement was accompanied by corneal melt and perforation. Despite aggressive medical and surgical treatment, both patients developed permanent loss of vision and ultimately expired.

Multiple Retinal Emboli and Medial Canthal Swelling Following Injection of Acellular Porcine Urinary Bladder Matrix for Hair Restoration.

Acellular porcine urinary bladder matrix promotes wound healing and is also used to stimulate hair growth. A 64-year-old female presented with acute-onset OD pain and decreased visual acuity after subcutaneous injection of acellular porcine urinary bladder matrix at the hairline. Fundus examination revealed multiple emboli at retinal arcade branch points, and fluorescein angiography demonstrated corresponding areas of peripheral nonperfusion. Two weeks later, external examination revealed new swelling of the right medial canthus without erythema or fluctuance, which was felt to possibly represent recruitment of vessels after occlusion in the facial vasculature. At 1-month follow up, visual acuity of the OD improved with resolution of right medial canthal swelling. Fundus examination was normal with no visible emboli. Herein, the authors present a case of retinal occlusion and medial canthal swelling following injection of acellular porcine urinary bladder matrix for hair restoration, which to the authors knowledge has not been previously reported.

National trends in surgical subspecialisation in ophthalmology in the USA.

BACKGROUND/AIMS: To assess surgical patterns in ophthalmology by subspecialty in the USA. METHODS: Ophthalmic surgeons were categorised as comprehensive/subspecialist based on billed procedures in the 2017-2018 Medicare Provider Utilization and Payment Data. Poisson regression models assessed factors associated with physicians performing surgeries in the core domain (eg, cataract extractions) and subspecialty domain. Models were adjusted for provider gender, time since graduation, geographical region, practice setting and hospital affiliation. RESULTS: There were 10 346 ophthalmic surgeons, 74.7% comprehensive and 25.3% subspecialists. Cataract extractions were performed by 6.0%, 9.9%, 21.0%, 88.1% and 95.3% of specialists in surgical retina, neuro-ophthalmology/paediatrics, oculoplastics, glaucoma and cornea, respectively. Retina specialists were more likely to perform cataract surgery if they were 20-30 or>30 years in practice (relative risk: 2.20 (95% CI: 1.17 to 4.12) and 3.74 (95% CI: 1.80 to 7.76), respectively) or in a non-metropolitan setting (3.78 (95% CI: 1.71 to 8.38)). Among oculoplastics specialists, male surgeons (2.71 (95% CI: 1.36 to 5.42)), those in practice 10-20 years or 20-30 years (1.93 (95% CI: 1.15 to 3.26) and 1.91 (95% CI: 1.11 to 3.27), respectively) and in non-metropolitan settings (3.07 (95% CI: 1.88 to 5.02)) were more likely to perform cataract surgery. Only 26 of the 2620 subspecialists performed surgeries in two or more subspecialty domains. CONCLUSIONS: There is a trend towards surgical subspecialisation in ophthalmology in the USA whereby some surgeons focus their surgical practice on subspecialty procedures and rarely perform surgeries in the core domain.

Use of computer-assisted surgery in the orbit.

PURPOSE: To present the application of computer-assisted surgery (CAS) in pre-operative planning, intra-operative navigation, and post-operative assessment as an adjunct tool in orbital surgery. METHODS: An IRB-approved, retrospective review was performed to identify patients who had undergone orbital surgery by a single surgeon from July 2013 to December 2019 with attention to pre-operative virtual surgical planning, intra-operative navigation, and post-operative assessment. The reasons and methods of CAS use were classified. RESULTS: The use of computer-assisted technologies was identified in 91 cases out of 464 orbital surgeries (19.6%). This included 23 (25.3%) orbital decompression surgeries, 39 (42.9%) fracture repairs, and 25 (27.5%) orbital tumors. In all cases, pre-, intra-, and post-operative CAS allowed for increased operative efficiency and safety with good outcomes. CONCLUSIONS: Use of CAS in orbital surgery can allow for complex radiographic analysis and in select cases is a great tool to add to the orbital surgeon's armamentarium.

Sensorineural Hearing Loss After Teprotumumab Therapy for Thyroid Eye Disease: A Case Report.

BACKGROUND AND OBJECTIVE: Teprotumumab is a fully human IgG1 monoclonal antibody against insulin-like growth factor-1 receptor (IGF-1R). It has been approved by the FDA to treat thyroid eye disease (TED) by reducing extraocular muscle and orbital fat volume. In clinical trials, hearing loss was noted as a side effect in 7 to 12% of patients, but no formal audiometric investigations of these patients were reported. Furthermore, the FDA and manufacturer offer no formal guidelines for audiometric monitoring. This case report is the first to describe sensorineural hearing loss (SNHL) in a patient undergoing treatment with teprotumumab. PATIENT: A 77-year-old woman presenting with bilateral SNHL after treatment with teprotumumab therapy for TED. INTERVENTION: Audiometric testing was performed due to worsening and prolonged SNHL after subsequent teprotumumab infusions. MAIN OUTCOME MEASURES: Word recognition scores, pure tone average. RESULTS: Audiometry after discontinuation of therapy showed moderate to moderate-severe SNHL with word recognition scores of 64% in the right ear and 68% in the left ear. CONCLUSIONS: There are currently no formal guidelines for routine audiograms before, during, and after infusion of teprotumumab. Given that such guidelines exist for ototoxic medications such as gentamicin and cisplatin, we strongly encourage audiometric monitoring for patients undergoing treatment with teprotumumab.

Transcriptomic Profiling of Control and Thyroid-Associated Orbitopathy (TAO) Orbital Fat and TAO Orbital Fibroblasts Undergoing Adipogenesis.

Purpose: Orbital fat hyperplasia commonly occurs in thyroid-associated orbitopathy (TAO). To understand molecular mechanisms underlying orbital adipogenesis, we used transcriptomics to compare gene expression in controls and patients with TAO, as well as in orbital fibroblasts (OFs) undergoing adipogenic differentiation. Methods: We performed bulk RNA sequencing (RNA-Seq) on intraconal orbital fat from controls and patients with TAO. We treated cultured OFs derived from patients with TAO with adipogenic media to induce adipogenesis. We used single nucleus RNA-Seq (snRNA-Seq) to profile treated and control OFs, identifying genes that are dynamically expressed during orbital adipogenesis in vitro, and compared these results to data from control and TAO orbital fat. Results: Gene expression profiles in control and TAO orbital fat are distinct. Signaling pathways including PI3K-Akt signaling, cAMP signaling, AGE-RAGE signaling, regulation of lipolysis, and thyroid hormone signaling are enriched in orbital fat isolated from patients with TAO. SnRNA-Seq of orbital fibroblasts undergoing adipogenesis reveals differential expression of the adipocyte-specific genes FABP4/5, APOE, PPARG, and ADIPOQ during adipogenic differentiation. The insulin-like growth factor-1 receptor and Wnt signaling pathways appear to be enriched early in adipogenesis. Gene modules that are enriched in TAO orbital fat are upregulated in orbital adipocytes during differentiation in vitro, whereas genes that are enriched in control orbital fat are enriched in undifferentiated OFs. Conclusions: We identified pathways enriched in TAO orbital fat, and dynamic changes in gene expression that occur during adipogenic differentiation of orbital fibroblasts. These findings may help guide functional studies of genes and pathways critical for orbital adipogenesis.

Temperature and species-dependent regulation of browning in retrobulbar fat.

Retrobulbar fat deposits surround the posterior retina and optic nerve head, but their function and origin are obscure. We report that mouse retrobulbar fat is a neural crest-derived tissue histologically and transcriptionally resembles interscapular brown fat. In contrast, human retrobulbar fat closely resembles white adipose tissue. Retrobulbar fat is also brown in other rodents, which are typically housed at temperatures below thermoneutrality, but is white in larger animals. We show that retrobulbar fat in mice housed at thermoneutral temperature show reduced expression of the brown fat marker Ucp1, and histological properties intermediate between white and brown fat. We conclude that retrobulbar fat can potentially serve as a site of active thermogenesis, that this capability is both temperature and species-dependent, and that this may facilitate regulation of intraocular temperature.

Chocolate Cysts Associated With Porous Polyethylene Orbital Implants.

Late-onset orbital hemorrhage is a rare complication of alloplastic implant use in orbital wall reconstruction following trauma. The authors report 3 patients with chocolate cysts presenting 3 to 9 years after orbital fracture repair with porous polyethylene implants. All patients were managed by implant removal and evacuation of cyst contents. Complete excision of the cyst was performed in 1 patient, while partial excision of the capsule was performed in 2 patients. Improvement of symptoms associated with the mass effects of the cyst was noted after surgical intervention. The authors also report the first case of orbital volume expansion from a chocolate cyst associated with a nonbarriered porous polyethylene implant. Delayed hemorrhage with capsule formation, although extremely rare, is a possible complication following orbital fracture repair with porous polyethylene implants.

Clinical Characteristics and Outcomes in Patients Undergoing Primary or Secondary Enucleation or Evisceration After Ocular Trauma.

PURPOSE: To investigate the frequency of primary versus secondary eye removal, frequency of enucleation versus evisceration, and characteristics and outcomes of patients undergoing these procedures after presenting with severe ocular trauma. PATIENTS AND METHODS: Retrospective chart review of patients presenting to the emergency department (ED) with severe eye trauma necessitating enucleation or evisceration between 2010 and 2018. RESULTS: There were 92 eyes from 90 patients included in our study. Twenty-seven percent of eyes underwent primary removal (n=25, 14 enucleation, 11 evisceration), while 73% of eyes underwent secondary removal (n=67, 50 enucleation, 17 evisceration). The mean patient age was 45.2 years (range 4.2-92.6); primary enucleation/evisceration patients were older on average than secondary eye removal patients [53.8 years (range 15.9-91.2) versus 42.2 years (range 4.2-91.6 years), p=0.04]. A median of 34 days passed between ED presentation and secondary enucleation/evisceration. Before undergoing secondary enucleation/evisceration, patients underwent a median of one ocular procedure (range 0-14) for various complications of trauma including orbital infection, choroidal or retinal tear or detachment, and wound dehiscence. Open globe injury repairs comprised 43 of the 92 total procedures (47%) performed prior to secondary enucleation/evisceration. Secondary enucleations/eviscerations required a median of seven clinic visits compared to two clinic visits required after primary surgeries (p<0.01). 10.7% of all patients (n=10) had at least one implant-related complication following enucleation/evisceration, with all but one of these patients being in the secondary enucleation/evisceration group. CONCLUSION: Primary enucleation or evisceration was performed in 27% of all eye removals, and enucleation was performed in 69.6% of all eye removals. Future research is warranted to determine if primary eye removal may be appropriate and when to consider enucleation versus evisceration.

Bicanalicular Intubation with the Kaneka Lacriflow for Proximal Lacrimal Drainage System Stenosis.

PURPOSE: The Kaneka Lacriflow CL (Lacriflow) bicanalicular lacrimal intubation system was evaluated as a self-retaining alternative to traditional modalities for stenting and dilation of the lacrimal drainage system in proximal lacrimal drainage system stenosis. PATIENTS AND METHODS: A retrospective chart review was conducted to assess the use of the Lacriflow system for treatment of patients with punctal and canalicular stenosis. Anesthesia type, operative time, and complications were assessed. RESULTS: In the time period evaluated, a total of 72 Lacriflow stents were placed in 45 patients, most commonly under intravenous sedation. Stents were left in place for a mean of 145 days, with 9 stents left in place for more than 1 year, and a mean follow-up time of 263 days. Early complications within 90 days included prolapse in 1 stent, symptomatic colonization for 2 stents, and corneal abrasion in 1 stent in a patient with anterior basement membrane dystrophy. Five additional stents developed colonization in the late postoperative period (four of which were more than 1 year after stent placement). The overall complication rate (per stent) at 3 months after surgery was 5.6% and at all follow-up time points was 13.9%. Operative times were significantly shorter for a cohort of patients undergoing bicanalicular intubation with the Ritleng system (P = 0.015). CONCLUSION: The Lacriflow bicanalicular stent can be easily placed without general anesthesia. Complication rates are comparable to other bicanalicular intubation systems, but increase with longer time that stents are left in place.

Effects of collagen crosslinking on porcine and human tarsal plate.

BACKGROUND: Floppy eyelid syndrome is a disorder in which the tarsal plate is easily distensible and is currently treated with conservative or surgical measures. Human tarsal plate contains type I collagen, which is crosslinked in corneal tissue as a treatment for keratoconus. We hypothesized that collagen crosslinking would similarly stiffen tarsal plate tissue and investigated this in porcine and human tarsal plate specimens. METHODS: Riboflavin-sensitized porcine and human tarsus samples were irradiated with ultraviolet-A light. Porcine experiments were analyzed with gross photographs, anterior segment optical computed tomography (AS-OCT) imaging, and tensile testing. A prospective study of human tarsus was performed on samples from patients undergoing wedge resection for floppy eyelid syndrome and was analyzed with AS-OCT and tensile testing. RESULTS: 73 porcine adnexa and 9 patients (16 eyelids) who underwent wedge excision were included in the study. Grossly, greater stiffness was observed in crosslinked porcine tissue. AS-OCT imaging in porcine tissue showed a distinct hyperreflective band in crosslinked specimens whose area and intensity increased with longer treatment time (P = 0.003); this band was also visible in crosslinked human specimens. Tensile testing was performed, but results were not statistically significant. CONCLUSIONS: AS-OCT imaging, which has not been previously described for tarsal plate, showed a characteristic change in crosslinked porcine and human specimens. Tissue stiffness was increased grossly, but changes in tensile properties were not statistically significant. Further study is warranted to determine relevance as a potential treatment for floppy eyelid syndrome.

Blood Collection within the Maxillary Sinus following Orbital Fracture Repair: The Impact of Mesh Implants and Drains.

This article aimed to assess the effects of (1) mesh (e.g., uncoated anatomic titanium plates) versus non-mesh (e.g., porous polyethylene-coated titanium sheets) implant materials and (2) drain placement on the accumulation of blood within the maxillary sinus following surgical repair of orbital floor fractures. Ninety-two patients who received orbital floor fracture repair between 2008 and 2014 were selected, with equal case numbers between categories: (1) non-mesh implant, without drain; (2) non-mesh implant, with drain; (3) mesh implant, without drain; and (4) mesh implant, with drain. Lesion-mapping software was used to measure blood and sinus volumes in postoperative computed tomographic images. Average postoperative maxillary sinus filling was 49% ± 29%. Average sinus filling was similar between mesh and non-mesh implant materials; this was true in cases with a drain (45 vs. 40%, respectively) and without (57 vs. 52%, respectively). Orbital drain placement was associated with a significant reduction ( p = 0.048) in maxillary sinus filling of 12%. Mesh and non-mesh implant materials allow for similar drainage of orbital blood into the maxillary sinus postoperatively. In the majority of cases, space is available within the maxillary sinus to allow for drainage of orbital blood. Intraoperative drain placement is associated with reduced blood pooling within the maxillary sinus, suggesting it allows for drainage of orbital blood to the outside world.

Similarity in Bilateral Isolated Internal Orbital Fractures.

PURPOSE: In evaluating patients sustaining bilateral isolated internal orbital fractures, the authors have observed both similar fracture locations and also similar expansion of orbital volumes. In this study, we aim to investigate if there is a propensity for the 2 orbits to fracture in symmetrically similar patterns when sustaining similar trauma. METHODS: A retrospective chart review was performed studying all cases at our institution of bilateral isolated internal orbital fractures involving the medial wall and/or the floor at the time of presentation. The similarity of the bilateral fracture locations was evaluated using the Fisher's exact test. The bilateral expanded orbital volumes were analyzed using the Wilcoxon signed-rank test to assess for orbital volume similarity. RESULTS: Twenty-four patients with bilateral internal orbital fractures were analyzed for fracture location similarity. Seventeen patients (70.8%) had 100% concordance in the orbital subregion fractured, and the association between the right and the left orbital fracture subregion locations was statistically significant (P < 0.0001). Fifteen patients were analyzed for orbital volume similarity. The average orbital cavity volume was 31.2 ± 3.8 cm on the right and 32.0 ± 3.7 cm on the left. There was a statistically significant difference between right and left orbital cavity volumes (P = 0.0026). CONCLUSIONS: The data from this study suggest that an individual who suffers isolated bilateral internal orbital fractures has a statistically significant similarity in the location of their orbital fractures. However, there does not appear to be statistically significant similarity in the expansion of the orbital volumes in these patients.

Is there more to the clinical outcome in posttraumatic reconstruction of the inferior and medial orbital walls than accuracy of implant placement and implant surface contouring? A prospective multicenter study to identify predictors of clinical outcome.

PURPOSE: Reconstruction of orbital wall fractures is demanding and has improved dramatically with the implementation of new technologies. True-to-original accuracy of reconstruction has been deemed essential for good clinical outcome, and reasons for unfavorable clinical outcome have been researched extensively. However, no detailed analysis on the influence of plate position and surface contour on clinical outcome has yet been published. MATERIALS AND METHODS: Data from a previous study were used for an ad-hoc analysis to identify predictors for unfavorable outcome, defined as diplopia or differences in globe height and/or globe projection of >2 mm. Presumed predictors were implant surface contour, aberrant implant dimension or position, accuracy of reconstructed orbital volume, and anatomical fracture topography according to the current AO classification. RESULTS: Neither in univariable nor in multivariable regression models were unfavorable clinical outcomes associated with any of the presumed radiological predictors, and no association of the type of implant, i.e., standard preformed, CAD-based individualized and non-CAD-based individualized with its surface contour could be shown. CONCLUSION: These data suggest that the influence of accurate mechanical reconstruction on clinical outcomes may be less predictable than previously believed, while the role of soft-tissue-related factors may have been underestimated.

Orbital fracture repair outcomes with preformed titanium mesh implants and comparison to porous polyethylene coated titanium sheets.

BACKGROUND: Restoration of orbital volume after internal orbital fractures can prevent enophthalmos. A variety of allografts are commonly used including titanium mesh with and without porous polyethylene coating. Some controversy exists over the use of uncoated titanium mesh in the orbit. Newer products contoured to the three dimensional orbital anatomy aim to improve reestablishment of the complex orbital shape though studies of outcomes with their use are limited. METHODS: A retrospective chart review was performed to evaluate surgical outcomes in all patients who underwent orbital fracture repair with DePuy/Synthes titanium MatrixMIDFACE prefabricated implants (PFTi) as compared with porous polyethylene/titanium hybrid implants (PPETi) including Stryker Medpor Titan, MTB, and BTB implants. Incidence of reoperation, diplopia, and movement restriction between PFTi and PPETi groups and the risk ratio of the above outcomes between implant types were compared. RESULTS: A total of 464 orbital implants were reviewed. Patients were divided by implant type with 195 patients receiving a PFTi implant and 269 patients receiving PPETi implant. (PFTi) and 269 had placement of a porous polyethylene/titanium hybrid implant. Despite statistically significant increased probability of utilization in more complex and delayed fractures, the PFTi implant showed no significant difference in complication profile or reoperation rate compared to the more commonly used PPETi. CONCLUSIONS: PFTi implants, designed to replicate the native orbital shape, have similar surgical outcomes and no difference in complication profile compared to standard porous polyethylene/titanium implants hybrid plates.

Virtual Fitting, Selection, and Cutting of Preformed Anatomic Orbital Implants.

PURPOSE: To evaluate the usage of preoperative digital anatomic implant evaluation in internal orbital fractures. METHODS: An IRB-approved review of cases of orbital fracture repair was conducted and cases where digital implant modeling was performed were selected for comprehensive review. The surgical time of these cases was also compared with surgeon and implant matched controls. RESULTS: A total of 25 patients and 26 orbits underwent preoperative virtual fitting and were reviewed. There were no complications or revision surgeries needed. Postoperative assessment demonstrated accuracy to the preoperative target with an average maximum deviation of 1.9 mm. CONCLUSIONS: Preoperative digital fracture assessment, implant manufacturer and size selection, and virtual cutting guide creation provides additional tools for orbital surgeons to achieve anatomic restoration without significant differences in operating time.

Implementing an electronic learning management system for an Ophthalmology residency program.

BACKGROUND: Medical educators, residents and administrators have increasing access to a large quantity of electronic resources. This content can augment and improve our teaching methods but can be difficult to consolidate and present. A multitude of electronic learning management systems are available to help organize and serve this content though never with small residency programs as the target userbase. As our residency program in Ophthalmology looked to consolidate our electronic resources and update our education methods, we evaluated and built an electronic learning management platform. RESULTS: Faculty were interviewed to determine features they would find useful in curriculum management system and then various systems were investigated for features, cost and ease of use. CONCLUSIONS: Our solution has been both cost-effective and successful. Resident satisfaction is high and faculty utilization has been increasing. We present many customizations that increased success. Consideration of the specific needs of a program is paramount to choosing a cost effective solution that will be well received.