The Rate of Retreatment in Patients treated with teprotumumab: A Multicenter Study of 119 Patients with 1 year Follow Up.

OBJECTIVE OR PURPOSE: To determine the rate of retreatment in patients who receive a full course of teprotumumab therapy for Thyroid Eye Disease (TED) and drivers of retreatment. DESIGN: Multi center, retrospective study SUBJECTS: All patients who received a full course of treatment and had available data at 1 year post initial treatment were included. METHODS: Charts were reviewed for the following information: age, gender, months since diagnosis of TED, smoking status, prior treatments. Further, the clinical activity score (CAS), proptosis and the Gorman diplopia score were reviewed at baseline, at the end of the first course and at baseline for the second course in those who received it. A logistic regression model was created to review the drivers of retreatment. MAIN OUTCOME MEASURES: Rate of retreatment and the drivers of retreatment. RESULTS: 119 patients were included from 3 centers across the US. The overall retreatment rate was 24% (29/119). There was no difference between the 3 sites (p = 0.6). In univariate analyses, at baseline, there was no difference in proptosis (p = 0.07), diplopia score (p = 0.4) or duration of TED (p = 0.4), between retreated and non-retreated patients. From the retreated group, 82% had a significant proptosis response (≥ 2 mms reduction from baseline) following their initial course, while 68% of patients had a clinically significant proptosis response in the non-retreated group (p = 0.16). The use of other treatments prior to the first infusion of teprotumumab and baseline thyroid dysfunction, were not significantly different between the retreated and non-retreated groups (p = 0.06 and 0.09, respectively). The mean (SD) difference between the end of first treatment and at baseline prior to second treatment (in those who received it) was 2 (2) for CAS, 2 mms (4) for proptosis and 1 (1) for diplopia. Age as the only significant driver of retreatment (p < 0.05). Retreated patients were 7 years older than their non retreated counterparts (age 60 vs 53 (p < 0.05). CONCLUSIONS: In patients receiving a full course of teprotumumab therapy, the rate of retreatment is 24%. Age is the only driver of retreatment.

Teprotumumab improves light sensitivity in patients with thyroid eye disease.

BACKGROUND: Teprotumumab, a novel IGF-1R antibody, has been shown to significantly reduce the signs of acute and chronic Thyroid Eye Disease (TED). Light sensitivity is a reported symptom in patients with TED. There is a lack of a prospective study that has explored the effects on light sensitivity in a large cohort of patients with acute and chronic TED following treatment with teprotumumab. METHODS: Consecutive patients who were diagnosed with TED and reported light sensitivity at baseline were considered for study eligibility. All patients had measurements of Visual Light Sensitivity Questionnaire-8 (VLSQ-8), proptosis, clinical activity score (CAS), and MRD1 (distance between the upper eyelid margin and corneal reflex, mm) and MRD2 (distance between the lower eyelid margin and corneal reflex, mm) before and after treatment. RESULTS: Ninety patients (41 acute, 49 chronic) met the inclusion criteria. The mean (SD) age was 47.3 (14.3). Eighty-six (95.6%) patients completed all 8 infusions. There was a significant reduction in the total score and across all categories of the VLSQ-8 (p <  0.01 for all). Seventy-two (80%) patients had a clinically significant improvement (≥2 reduction) in at least one category. There was no significant difference in the total VLSQ-8 score between the acute and chronic group (p = 0.8). CONCLUSION: Teprotumumab improves light sensitivity in patients with acute and chronic TED. The results of this study highlight that the improvements in light sensitivity following treatment are not directly related to the mechanical changes in TED, suggesting another underlying mechanism is potentially involved.

Teprotumumab for thyroid eye disease in patients with hypothyroid/euthyroid state: a multicenter case series.

BACKGROUND: Teprotumumab, a novel IGF-1R antibody was recently shown to significantly reduce the signs of acute and chronic thyroid eye disease (TED) related to hyperthyroidism. Given the lower incidence of TED associated with hypothyroidism / euthyroidism, there is a paucity of data regarding the efficacy of teprotumumab in this group. METHODS: In this multicenter study, consecutive patients who had been diagnosed with TED, presenting with either hypothyroidism or euthyroidism as their baseline thyroid dysfunction and treated with teprotumumab were included. All patients had measurements of proptosis, clinical activity scores (CAS), diplopia scores and four-point strabismus scores before and after therapy. RESULTS: Twenty-six patients met the inclusion criteria. Mean age was 48 ± 14 years old and mean duration of TED prior to treatment was 31 ± 43 months. All patients received 8 infusions. Mean (SD) reduction in proptosis for study orbits was 2.7 mm (1.8) (p < 0.05) and 1.8 mm (2.0) for the fellow orbit (p < 0.05). In the study orbit, mean (SD) CAS was 2.3 (1.3) before therapy and 1.0 (1.0) following therapy (p < 0.05). At baseline, mean (SD) diplopia score was 1.2 (1.1) and 0.9 (1.1) following therapy (p < 0.05). CONCLUSION: Teprotumumab reduces proptosis and inflammation in patients presenting with TED associated with hypothyroidism and euthyroidism. The results of this study highlight the potential for teprotumumab therapy in this subgroup and also provide a unique insight into the potential role of the IGF-1R in these patients.

Change in lacrimal gland volume and aqueous tear production following treatment with teprotumumab.

BACKGROUND: Dry eye syndrome occurs in up to 85% of patients with thyroid eye disease (TED). Lacrimal gland enlargement correlates with subjective tearing and a reduction in quality of life in patients with TED. METHODS: In this prospective longitudinal study, patients presenting for the treatment of TED were considered for eligible. Primary outcomes included a change in the volume of the lacrimal gland and the production of tears following treatment with teprotumumab. The volume of lacrimal glands and proptosis was calculated using 3D volumetric analysis. Tear production was measured by Schirmer's test and associated symptoms were assessed using the VLSQ-8. The orbit with the most proptosis was designated the study orbit and the contralateral orbit was designated the fellow orbit. RESULTS: Twenty patients were included. Mean (SD) age was 61 (18) and mean duration of TED prior to therapy was 48 months (47). Lacrimal gland volume in the study orbit decreased from 768 mm3 (288) to 486 mm3 (173) (p < 0.01) following therapy. For the fellow orbit, volume reduced from 637 mm3 (261) to 379 mm3 (147) (p < 0.01). Schirmer's test reading (STR) in the study orbit increased from 14.5 mm (8.2) to 23 mm (10) (p < 0.01) (59%) following treatment. In the fellow orbit, STR increased from 12.7 mm (7) to 21 mm (9) post therapy (69%) (p < 0.01). There was a significant improvement on all parts of the VLSQ-8. CONCLUSION: Teprotumumab significantly reduces TED related expansion of the lacrimal gland, increases tear production, and improves dry eye symptoms.

A Review of Midface Aging.

PURPOSE: To review and summarize studies on the anatomy and involutional changes of the midface. METHODS: A PubMed search was performed searching for studies on the anatomy and involutional changes concerning the midface. RESULTS: The anatomy of the midface is complex. Studies of involutional change vary in scientific quality and have conflicting results. However, it appears that among the more common changes, there is a decrease in the maxillary and pyriform angle, with changes to the orbital floor position. Further, there appears to be an inferior migration of the fat compartments of the midface during aging, exacerbating the hollow of the palpebromalar groove and causing a deepening of the nasojugal groove. Changes to the volume of the buccal extension of the buccal fat pad exacerbate these changes and contribute to the gestalt changes associated with facial aging. Here, we review the major characteristics of soft tissue and bony changes on the midface, with special reference to their anatomic relationships. CONCLUSIONS: The major findings characterizing midface aging are related largely to the soft tissue. However, more robust studies are required to quantify these changes and to appraise their impact on the overall manifestation of aging.

Teprotumumab for the Treatment of Recalcitrant Thyroid Eye Disease.

PURPOSE: Teprotumumab, an insulin-like growth factor 1 receptor monoclonal antibody, is FDA-approved to treat thyroid eye disease (TED). The initial clinical trials excluded patients with previous orbital irradiation, surgery, glucocorticoid use (cumulative dose >1 gm), or prior biologic treatment. Information on the use of teprotumumab for patients who failed prior therapy is limited. Our purpose is to characterize the efficacy of teprotumumab for the treatment of recalcitrant TED. METHODS: This is a multicenter retrospective study of all patients treated with teprotumumab for moderate-to-severe TED after failing conventional therapy with corticosteroids, orbital radiation, surgical decompression, biologics, or other steroid-sparing medications. Treatment failure was defined as an incomplete response to or reactivation after previous treatment. Only patients who received at least 4 infusions of teprotumumab were included in the analysis. Primary outcome measures comprised proptosis response (≥2 mm reduction in the study eye without a similar increase in the other eye), clinical activity score (CAS) response (≥2-point reduction in CAS), and diplopia response (≥1 point improvement in Gorman diplopia score in patients with baseline diplopia) following treatment. Adverse events and risk factors for recalcitrant disease were also evaluated. RESULTS: Sixty-six patients were included in this study, 46 females and 20 males. Average age was 59.3 years (range 29-93). The mean duration of disease from TED diagnosis to first infusion was 57.8 months. The proptosis, CAS, and diplopia responses in this recalcitrant patient population were 85.9%, 93.8%, and 69.1%, respectively. Patients experienced a mean reduction in proptosis of 3.1 ± 2.4 mm and a mean improvement in CAS of 3.8 ± 1.6. Patients who underwent prior decompression surgery experienced a statistically significant decrease in diplopia response (46.7% vs. 77.5%, p = 0.014) and proptosis response (75.0% vs. 90.9%, p = 0.045) when compared with nondecompression patients. Additionally, there were no significant differences in proptosis, CAS, and diplopia responses between patients with acute (defined as disease duration <1 year) versus chronic (disease duration ≥1 year) TED. While most adverse events were mild to moderate, 4 patients reported serious adverse events related to persistent hearing loss. CONCLUSIONS: Patients with recalcitrant TED demonstrated a significant improvement after teprotumumab in each of the primary study outcomes. The degree of proptosis reduction, diplopia response, and CAS improvement in the recalcitrant group were similar to those of treatment-naïve patients from the pivotal clinical trials. Patients with a prior history of orbital decompression, however, demonstrated poor improvement in diplopia and less reduction in proptosis than surgery naïve patients. These results indicate that teprotumumab is a treatment option for the treatment of patients with TED recalcitrant to prior medical therapies.

The Management of Lumps, Bumps, and Contour Irregularities of the Lower Eyelid and Cheek After Poor Outcome Fat Transfer.

BACKGROUND: The increasing popularity of fat transfer (FT) to the lower eyelids has led to an increase in unwanted lumps, bumps, and contour irregularities (LBCs). Few studies have addressed the management of LBCs. OBJECTIVES: The aim of this study was to address the management of LBCs. METHODS: In this retrospective review, charts of all patients presenting for evaluation of LBCs following FT procedures to the lower eyelid were reviewed. Clinical characteristics on presentation and surgical findings were evaluated. Patient postoperative clinical course and complications were also documented. RESULTS: Forty-eight patients were included (45 women and 3 men), with an average follow-up of 14 months (range, 5-24 months). In 65%, LBCs manifested above the lower orbital rim (AR) and in 35% they were noted AR and below the rim (AR/BR). The type of contour deficits noted were a solitary nodule (SN) in 54%, a mixed picture (MP) in 23%, diffuse enlargement (DE) in 17%, and multiple nodules (MNs) in 6%. Combining lesion location and type of contour deficit, the most common presentation was an SN-AR in 22 patients (46%), followed by an MP-AR/BR in 8 patients (17%), and a DE-AR/BR in 5 patients (10%). Surgical findings revealed that grafted fat is consistently found separate from native eyelid/orbital fat, and within the orbicularis muscle when AR, and within the orbicularis muscle or the deep suborbicularis oculi fat when BR. CONCLUSIONS: LBCs tend to manifest in characteristic patterns with a predilection for an AR location. Recommendations on the diagnosis and management of these lesions are provided.

Teprotumumab Efficacy, Safety, and Durability in Longer-Duration Thyroid Eye Disease and Re-treatment: OPTIC-X Study.

PURPOSE: To evaluate teprotumumab safety/efficacy in patients with thyroid eye disease (TED) who were nonresponsive or who experienced a disease flare. DESIGN: The Treatment of Graves' Orbitopathy to Reduce Proptosis with Teprotumumab Infusions in an Open-Label Clinical Extension Study (OPTIC-X) is a teprotumumab treatment and re-treatment trial following the placebo-controlled teprotumumab Phase 3 Treatment of Graves' Orbitopathy (Thyroid Eye Disease) to Reduce Proptosis with Teprotumumab Infusions in a Randomized, Placebo-Controlled, Clinical Study (OPTIC) trial. PARTICIPANTS: Patients who previously received placebo (n = 37) or teprotumumab (n = 14) in OPTIC. METHODS: OPTIC nonresponders or those who flared (≥2-mm increase in proptosis, ≥2-point increase in clinical activity score [CAS], or both) during follow-up were treated for the first time (previous placebo patients) or re-treated with teprotumumab in OPTIC-X with 8 infusions over 24 weeks. MAIN OUTCOME MEASURES: Proptosis response and safety. Secondary outcomes included proptosis, CAS, subjective diplopia, and quality-of-life. RESULTS: Thirty-three of 37 placebo-treated OPTIC patients (89.2%) became proptosis responders (mean ± standard deviation, -3.5 ± 1.7 mm) when treated with teprotumumab in OPTIC-X. The responses were equivalent to the OPTIC study. In these responders, proptosis, CAS of 0 or 1, and diplopia responses were maintained in 29 of 32 patients (90.6%), 20 of 21 patients (95.2%), and 12 of 14 patients (85.7%), respectively, at follow-up week 48. The median TED duration was 12.9 months versus 6.3 months in those treated with teprotumumab in the OPTIC study. Of the 5 OPTIC teprotumumab nonresponders re-treated in OPTIC-X, 2 responded, 1 showed a proptosis reduction of 1.5 mm from OPTIC baseline, and 2 discontinued treatment early. Of the OPTIC teprotumumab responders who experienced flare, 5 of 8 patients (62.5%) responded when re-treated (mean proptosis reduction, 1.9 ± 1.2 mm from OPTIC-X baseline and 3.3 ± 0.7 mm from OPTIC baseline). Compared with published double-masked trials and their integrated follow-up, no new safety signals were identified. Mild hearing impairment was reported; 4 events occurred during the first course of treatment, and 2 events reoccurred after re-treatment. CONCLUSIONS: Patients with TED of longer disease duration responded similarly to those treated earlier in the disease course. Patients with an insufficient initial response or flare may benefit from additional teprotumumab therapy. No new safety risk was identified; however additional postmarketing pharmacovigilance is ongoing.

A Paradigm Shift in the Management of Thyroid Eye Disease How Teprotumumab Has Changed the Therapeutic Interface.

BACKGROUND: Teprotumumab, a monoclonal antibody that blocks the insulin-like growth factor-1 receptor, has recently been approved by the US Food and Drug Administration (FDA) for the treatment of thyroid eye disease (TED). Since its approval, aside from data on the safety and clinical efficacy of teprotumumab from Phase-2 and Phase-3 trials, only a handful of reports have been published regarding its use in the wider population. In this review, we briefly describe the mechanism of action of teprotumumab and review the literature to provide an overview of published clinical experience. This information was used to provide recommendations for patient selection, management of patient expectations, infusion details and site options, tips to optimize the authorization process, and how to monitor and mitigate side effects. EVIDENCE ACQUISITION: A systemic review of the literature was performed regarding teprotumumab, focusing on its mechanisms of action and published reports on its use on patients with TED. A review of Embase, Medline (PubMed), Web of Science, and Google Scholar was conducted. RESULTS: Clinical experience following the approval of teprotumumab has confirmed its efficacy in reducing inflammation and proptosis in patients with acute TED (<2 years). The reduction in proptosis occurs due to a reduction in orbital fat and muscle volume. Furthermore, there is evidence for its use in patients with compressive optic neuropathy. There are also reports that show its efficacy in reducing proptosis, inflammation, and diplopia in patients with chronic TED (>2 years). Teprotumumab was associated with side effects, such as muscle spasm, hearing loss, and hyperglycemia. To date, 2 case reports have shown a possible association with flares of inflammatory bowel disease. CONCLUSIONS: Teprotumumab is a powerful therapeutic option for the treatment of TED. Clinical experience following FDA approval has demonstrated efficacy in treating patients with acute and chronic TED. It is the only therapeutic option that has been shown to reduce orbital soft tissue expansion in TED. However, it is expensive, and sometimes, obtaining insurance authorization can be time consuming and difficult. Further work will reveal its full side effect profile and help to establish its role in the armamentarium used to treat TED.

Expert Consensus on the Use of Teprotumumab for the Management of Thyroid Eye Disease Using a Modified-Delphi Approach.

BACKGROUND: Teprotumumab is the first treatment for thyroid eye disease (TED), a debilitating autoinflammatory condition, approved by the Food and Drug Administration in the United States, which reduces proptosis and improves quality of life. In the absence of guidelines, clinical recommendations were developed for using teprotumumab in patients with TED in the United States. METHODS: A 3-round modified-Delphi panel was conducted between October 2020 and February 2021 with experts in the management of patients with TED. Key areas regarding the use of teprotumumab were investigated, including eligible patient populations, concomitant treatments, and assessment of response and adverse events. This used 2 survey rounds via an online questionnaire, where statements were scored using 9-point Likert scales. Statements with conflict were included in the third round, involving a consensus meeting via videoconference. RESULTS: Consensus was obtained for all statements (n = 75); of which, 56% were revised to enable agreement of the group. The consensus meeting provided agreement regarding which populations should receive teprotumumab therapy, including all adult patients with TED with a clinical activity score of ≥4. Treatment with teprotumumab can also be considered for TED patients displaying the following characteristics: a CAS of <3, lid retraction of ≥2, and mild or early optic neuropathy with close clinical observation. Further recommendations included suitability of treatment for those beyond 16 months following the initial diagnosis of TED, low CAS concomitant treatment with steroids in some cases, retreatment for those who have relapses, and finally a recommendation to continue therapy for all 8 infusions despite the lack of response by the fourth infusion. CONCLUSIONS: This work constitutes the first consensus on guidelines for the use of teprotumumab. The modified Delphi approach involved physicians with significant experience with the clinical use of teprotumumab, and recommendations were based on current evidence.

Thrombogenicity of Hyaluronic Acid Fillers: A Quantitative Thrombodynamics Study.

PURPOSE: At present, there is a paucity of data regarding the thrombogenicity of hyaluronic acid fillers (HAFs). This article quantitatively analyses the thrombogenicity of 2 commonly used HAFs: Restylane Lyft and Juvéderm Ultra. METHODS: Thrombogenicity was assessed using the Thrombodynamics Analyzer System and plasma obtained from healthy controls. Following the addition of HAFs or control, spontaneous clot formation time, initial rate of clot growth, average rate of clot growth over 30 minutes, and clot size at 30 minutes was measured for each sample. The median of differences between each group were analyzed. RESULTS: Nine individuals with a mean (SD) age of 37 (17) years, participated in the study. Initial rate of clot growth was significantly lower in plasma mixed with Juvéderm compared to control (p = 0.008) or Restylane (p = 0.038). The average rate of clot growth more than 30 minutes was significantly lower in both HAF groups (Restylane vs. control p = 0.038; Juvéderm vs. control p = 0.008), there was no significant difference between HAF groups (p = 0.635). Final clot size was significantly smaller with Juvéderm (p = 0.038 vs. control and p = 0.013 vs. Restylane). Spontaneous clot formation time did not significantly change with the addition of either HAF. CONCLUSIONS: Juvéderm significantly reduces the initial rate of clot growth, the average rate of clot growth more than 30 minutes, and clot size, whereas the addition of Restylane decreases the average rate of clot growth without affecting overall clot size in healthy individuals.

Changes to Eye Whiteness and Eyelid/Brow Position With Topical Oxymetazoline in Aesthetic Patients.

BACKGROUND: Oxymetazoline hydrochloride 0.1% ophthalmic solution has recently been approved in the United States for the treatment of ptosis. OBJECTIVES: The aim of this study was to assess the upper and lower eyelid position as well as the brow position and the color of the sclera following the ophthalmic administration of oxymetazoline hydrochloride 0.1%. METHODS: In this prospective cohort study, consecutive patients presenting with ptosis received topical oxymetazoline 0.1%. The primary outcome was measurement of the upper eyelid height (margin-to-reflex distance 1 [MRD1]) and lower eyelid height (MRD2) relative to the center of pupil, along with assessment of brow height, measured on photographs at baseline and 2 hours after instillation of oxymetazoline. The secondary outcome was the assessment of the color of the sclera (eye whiteness) before and after treatment with a novel color space algorithm. RESULTS: Twenty-nine patients participated in the study. The mean [SD] MRD1 at baseline was 2.3 [0.6] mm. At 2 hours following oxymetazoline treatment, the mean MRD1 significantly increased to 4.2 [0.9] mm (P < 0.01). The mean MRD2 also significantly increased from 5.3 [0.9] mm to 5.7 [1.0] mm (P < 0.01). Brow position did not change with treatment (P = 0.4). Following treatment, the eye sclera became significantly whiter, with a mean ΔEab (color change) of 9.7 [3.9], with 57 out of 58 eyes experiencing a significant change in color. A change of ΔEab ≥2 is considered visually perceptible to the human eye. CONCLUSIONS: Within 2 hours of use, oxymetazoline significantly improves the size of the palpebral aperture (MRD1 + MRD2) and also makes the eye appear significantly whiter.

Quantifying the Digestion of Cross-Linked Hyaluronic Acid Fillers With Hyaluronidase.

BACKGROUND: Adverse events due to hyaluronic acid fillers (HAFs) may be treated with hyaluronidase, an enzyme that cleaves bonds within hyaluronic acid. This study reviews the efficacy of currently available hyaluronidase preparations in breaking down commercial, cross-linked HAFs. METHODS: Three HAFs were used in this study (Restylane, Juvederm Voluma, and Belotero [BEL] Balance). A laser-based particle size analyzer (Malvern Mastersizer 3000) was used to calculate particle sizes in untreated HAFs (controls) and those treated with 450 units of hyaluronidase (Hylenex) for 5 and 30 minutes. RESULTS: Particle size analysis revealed that when Restylane was treated with hyaluronidase for 5 minutes, the average particle size reduced modestly, from 472 to 440 µm. At 30 minutes, the average particle size was 419 µm. For Juvederm, the average size of particles reduced from 703 µm in controls to 676 µm after treatment with hyaluronidase for 5 minutes and 635 µm after treatment for 30 minutes. For Belotero, the average size of control particles was 410 µm, reducing to 376 µm after treatment with hyaluronidase for 5 minutes and 345 µm after treatment for 30 minutes. CONCLUSION: After treatment with hyaluronidase for up to 30 minutes, there was only a modest breakdown of all 3 HAFs used. The results of this study raise questions regarding the efficacy of hyaluronidase in degrading cross-linked HAFs.

Generation of Filler Emboli as a Mechanism for Filler-Related Blindness.

BACKGROUND: Intra-arterial injection of fillers can lead to occlusion of the ophthalmic artery or its branches supplying the retina or the optic nerve. The mechanism through which this occurs is incompletely understood. We investigated the possibility of generating microparticles after injecting commercially available fillers into a flowing system in vitro. METHODS: Three hyaluronic acid fillers and one calcium hydroxylapatite filler were injected into an artificial saline flow system mimicking arterial systolic blood pressure and corresponding to the diameter of the facial artery. All the saline at the end of the tube was collected, centrifuged, and inspected for filler particles. RESULTS: After injection into the system, all fillers immediately disintegrated into small particles that were carried downstream with the flow of the saline. The saline at the end of the tube contained collections of filler. CONCLUSION: Hyaluronic acid and hydroxylapatite fillers break up into small particles immediately after injection into a flowing system, generating emboli rather than a column of filler. The results of this study lead us to hypothesize another potential mechanism leading to filler-related blindness.

The Force Required to Inject a Column of Filler Through Facial Arteries.

BACKGROUND: Injectable fillers have become an integral part of facial rejuvenation, but vascular occlusion is a dreaded complication of such injections. OBJECTIVE: To determine the force required by the fingertip onto the plunger of the syringe to cause retrograde migration. METHODS: In this cadaver study, twelve 2-cm arterial segments and 4 fillers were tested. Injection pressure required to force a column of filler for 1 cm was measured. Five oculoplastics specialists were subsequently recruited and asked to inject the filler at a typical injection pressure. RESULTS: The nonhyaluronic acid filler required significantly more pressure to cause propagation of the material compared with all other fillers (p < .01). None of the other fillers differed significantly from each other. Typical injection pressures generated by experienced injectors were significantly lower than that required to cause propagation of filler at the desired velocity and significantly lower than mean arterial pressure. Measured pressure required to cause filler propagation was well within the normal range of the finger strength that can be generated by humans. CONCLUSION: Typical injection pressures from fingertip to plunger are lower than required to cause propagation of filler intravascularly.

The Adnexal Phenotype of Sagging Eye Syndrome.

PURPOSE: The sagging eye syndrome (SES) describes a condition that presents with age-related distance esotropia, alone or in combination with cyclovertical strabismus. It has a high prevalence in those aged over age 40 years presenting with binocular diplopia. The authors aim to characterize the adnexal phenotype of those who have been diagnosed with SES. METHODS: In this case-control study, patients were recruited from a prospectively maintained clinical and imaging database. The inclusion criteria required that subjects be above the age of 18 years and have a diagnosis of age-related distance esotropia or cyclovertical strabismus due to SES. Age-matched controls were selected from a validated database of normal faces that were not affected by any medical or surgical conditions. The margin to reflex distance from the upper eyelid, margin to reflex distance to the lower eyelid, the tarsal platform show, intracanthal distance, and inferior scleral bow were measured. Differences in the measurements between patients and controls were analyzed using a 2-tailed Student t tests. RESULTS: Twenty-two patients and 22 age-matched controls (11 males and 11 females per group) were included for study. Females with SES had a significantly greater margin to reflex distance to the lower eyelid and inferior scleral bow, with a lower tarsal platform show and margin to reflex distance from the upper eyelid than controls. Male patients with SES had a significantly greater margin to reflex distance to the lower eyelid and inferior scleral bow with a significantly lower margin to reflex distance from the upper eyelid and tarsal platform show than controls. DISCUSSION: This study supports the growing body of evidence which suggests that the SES represents age-related mechanical changes in the orbit that manifest as a specific adnexal phenotype.

Photochemical Collagen Cross-Linking Reverses Elastase-Induced Mechanical Degradation of Upper Eyelid Tarsus.

INTRODUCTION: The floppy eyelid syndrome describes an eyelid disorder characterized by floppy tarsal plates that may be caused by a loss of elastin. The authors attempted to create floppy eyelids by digesting elastin from cadaveric tarsus and then treated them with cross-linking using ultraviolet A and riboflavin. METHODS: Nine right and 9 left upper eyelids were excised from cadavers. Four vertical strips of central tarsus were removed from each eyelid. One strip of tarsus from each eyelid was treated with 10 units/ml of elastase for 2 hours. Another tarsal strip from each eyelid was immersed in normal saline for 2 hours (control). A third strip from the same eyelid was cross-linked using ultraviolet A at 6 mW/cm for 18 minutes. Finally, a fourth strip of tarsus was cross-linked in the same manner following treatment with elastase for 2 hours. A microtensile load cell was used to measure the Young modulus (stiffness) of each tissue. RESULTS: Mean (standard deviation) Young modulus for controls (18.9 ± 3.6 MPa) was significantly higher than samples treated with elastase alone (6.6 ± 3.8 MPa, p <0.01). Samples that were treated with cross-linking after elastase had a mean (standard deviation) Young modulus of 26 ± 2.3 MPa, while those treated with cross-linking alone had a mean (standard deviation) Young modulus of 34 ± 0.15 MPa. The differences in stiffness between all groups were significant (p <0.01). DISCUSSION: Treatment with elastase significantly reduces the stiffness of tarsal plates. This effect is reversed by cross-linking, raising the possibility of using this modality for the treatment of FES.

Examining the Role of Retrobulbar Hyaluronidase in Reversing Filler-Induced Blindness: A Systematic Review.

PURPOSE: To provide a systematic review of the literature concerning retrobulbar hyaluronidase injections as a treatment for hyaluronic acid gel filler-induced blindness and evaluate the level of evidence for this proposed therapy. METHODS: The authors performed a search of English language articles published on the use of retrobulbar hyaluronidase to reverse vision loss precipitated by hyaluronic acid gel fillers. Articles reviewed included case reports/series, experimental investigations, expert opinion commentaries, and major reviews. To date, there have been no case-control, cohort, or randomized control studies to evaluate this treatment. Five anecdotal descriptions of hyaluronic acid gel filler blindness treated specifically with retrobulbar hyaluronidase were identified, for a total of 9 patients. One hundred twelve articles in total on this treatment and related topics, including filler-induced blindness and alternative treatments, were identified and reviewed. RESULTS: Of the 9 documented cases of patients treated with retrobulbar hyaluronidase for hyaluronic acid-induced blindness, visual improvement was demonstrated in 2 cases. The successes, however, are undermined by inconsistent pretreatment ophthalmic assessment and documentation. Animal studies demonstrate mixed results. Laboratory studies document the inability of hyaluronidase to cross the optic nerve sheath. CONCLUSIONS: There is not currently enough evidence to support retrobulbar hyaluronidase as a treatment for filler-induced blindness. Additional studies are needed to further evaluate its efficacy and explore alternative treatments.

Orbital Volume Increases With Age: A Computed Tomography-Based Volumetric Study.

OBJECTIVE: The aim of the study was to determine whether the bony orbital volume (BOV) changes with age in males and females. METHODS: This case-control study reviewed high-resolution (<1-mm slices) computed tomography (CT) scans of consecutive patients seen for 4 years. The scans were requested as part of the patient's routine care for symptoms related to sinus symptoms. Eligible participants were adults aged between 18 and 30 years and 60 and 75 years. Exclusion criteria included previous surgery, any medical conditions that might affect the bone or soft tissue of the orbit, and any abnormalities seen on imaging. Male patients aged between 18 and 30 years were compared with males aged 60 to 75 years. The same was done for females. The main outcome measure was measurement of the BOV. Both orbits of each patient were included using the generalized estimating equation, to avoid any bias from correlation between 2 orbits of the same patient. RESULTS: A total of 240 orbits from 120 patients were used for this study. Each age group contained 30 patients. There were no significant differences in the ages between males and females in each age category (P = 0.88 for ages 20-30 years and P = 0.74 for ages 60-75 years). The mean (SD) BOV for females aged between 20 and 30 years was 19,153.69 mm (3776.21), whereas that for females aged between 60 and 75 years was 20,939.38 mm (2837.34). The difference between the groups was significant (Pr(>|W|) = 0.05). The mean (SD) BOV for males aged between 20 and 30 years was 22,2721 mm (2977.35), whereas that for males aged between 60 and 75 years was 22,892.92 mm (2389.46) (Fig. 1). The difference between these 2 groups was not significant (Pr(>|W|) = 0.40). The mean BOV was significantly greater for males than females (P ≤ 0.01) across both age groups. CONCLUSIONS: This study found that female orbits expand with age, whereas male orbits showed no significant changes. Changes to the orbital volume in females may contribute to the appearance of aging.

Noninflammatory Thyroid Eye Disease.

PURPOSE: Patients presenting with thyroid eye disease (TED) usually follow a well-defined self-remitting course characterized by an active inflammatory phase followed by an inactive fibrotic phase. We present 3 cases where patients presented primarily with signs of progressive fibrosis and no signs of prior active inflammation. METHODS: We reviewed the clinical notes and investigations of 3 patients who presented to our center between January 2015 and August 2017. RESULTS: All patients included in the study presented primarily with severe, progressive fibrosis without evidence of a previous active inflammatory condition. Although there were no signs of inflammation, each case was progressive, with 2 of the cases developing dysthyroid optic neuropathy that was relatively recalcitrant. We found that these patients were older than the general population of TED patients and that their disease course represents a departure from the common narrative. CONCLUSIONS: This subgroup of TED patients do not conform to the typical inflammatory natural history of TED. We propose that the heterogeneity of the orbital fibroblast pool and their function may be different in this subgroup. Further work will be required to reveal the pathophysiology of this atypical TED process, potentially revealing links between aging and the inflammatory mediators in TED.