Traumatic Optic Neuropathy Treatment Trial 2 (TONTT-2): evaluating the efficacy of different doses of erythropoietin - a multicentre, randomised, double-blind clinical trial.

AIM: The aim is to compare the efficacy and safety of three different weight-adjusted intravenous erythropoietin (EPO) doses in patients with indirect traumatic optic neuropathy (TON). METHODS: This study is a multicentre, randomised, parallel-group, double-blind, dose-finding trial on patients aged ≥7 years with a confirmed diagnosis of indirect TON in ≤3 weeks. The trial had a 3-day treatment period and a 3-month follow-up period. Patients were randomly allocated (1:1:1) to receive EPO at doses of 900 IU/kg (300 IU/kg/day), 1800 IU/kg (600 IU/kg/day) or 3600 IU/kg (600 IU/kg/day on presentation and then 1 month later) EPO. The changes in the best-corrected visual acuity (BCVA), colour vision and relative afferent pupillary defect (RAPD) were assessed. RESULTS: Out of 118 eligible patients, 95 were randomised and 93 (31 in each group) completed the follow-ups. Three groups were not different regarding baseline BCVA (p=0.66), colour vision (p=0.25) and RAPD (p=0.79). All three groups showed a significant improvement of BCVA and RAPD with no significant differences among the groups. Colour vision showed a significant improvement only in the group with 3600 IU/kg EPO (p=0.005), even though final colour vision was not significantly different between the groups (p=0.49). Initial vision of no light perception (OR=7.79 (95% CI: 2.98 to 20.36), p<0.001), older age (OR=4.76 (95% CI: 1.92 to 11.76), p<0.001), longer trauma-treatment interval (OR=2.72, 95% CI: 1.16 to 6.33, p=0.02) and posterior orbital fractures (OR=2.63 (95% CI: 1.13 to 6.13), p=0.02) led to a significantly worse visual recovery. CONCLUSION: Increasing dose of EPO in patients with TON did not result in a better BCVA, colour vision and RAPD improvement. TRIAL REGISTRATION NUMBER: NCT03308448.

Type and Frequency of Misdiagnosis and Time Lag to Diagnosis in Patients with Chronic Progressive External Ophthalmoplegia.

Purpose: Since ptosis is an early feature of chronic progressive external ophthalmoplegia (CPEO), patients are commonly misdiagnosed with other causes of ptosis. This study aims to report the type and frequency of misdiagnosis and time lag to diagnosis and the palpebral fissure transfer (PFT) procedure in patients with CPEO. Methods: This is a retrospective analysis of consecutive patients with CPEO who underwent PFT between 2006 and 2017. The data on previous diagnoses and treatments, age at definitive diagnosis of CPEO, and clinical manifestations were recorded. While the diagnosis of CPEO was based on clinical examination, 75% (24/32) of patients had undergone a confirmatory muscle biopsy and genetic tests. Results: There were 32 patients (19 females) with a mean age of 24.8 years (range, 13-36) at the final diagnosis and 34.1 years (range, 15-56) at the time of PFT. Also, 78% (25/32) of patients had been initially misdiagnosed with congenital ptosis (60%; 15/25) and ocular myasthenia gravis (OMG) (40%; 10/25). The majority of patients (20/32) had one to three previous eyelid surgical procedures, of which 90% (18/20) were performed before the definitive diagnosis of CPEO. The mean time lag from the first surgical procedure to CPEO diagnosis and PFT was 6.2 and 14.7 years, respectively. Conclusion: In a referral center, 78% of the patients with CPEO were initially misdiagnosed with congenital ptosis and OMG, and 56% of them underwent ptosis repair before the diagnosis. While the onset of the disease was in the first or second decades of life, diagnosis was delayed up to a mean age of 25 years. Reviewing early family photos and paying attention to other signs of CPEO could prevent misdiagnosis.

Risk Factors of COVID-19 associated mucormycosis in Iranian patients: a multicenter study.

BACKGROUND: To evaluate the demographic, clinical, and prognostic characteristics of patients diagnosed with COVID-19-associated mucormycosis (CAM) in Iranian patients. METHODS: This prospective observational study was conducted in 8 tertiary referral ophthalmology centers in different provinces of Iran during the fifth wave of the COVID-19 pandemic. All patients were subjected to complete history taking and comprehensive ophthalmological examination and underwent standard accepted treatment strategy based on the disease stage. RESULTS: Two hundred seventy-four CAM patients (most were males (150, 54.7%)) with a mean age of 56.8 ± 12.44 years were enrolled. Patients with a history of cigarette smoking (Adjusted Odds Ratio (AOR) = 4.36), Intensive Care Unit admission (ICU) (AOR = 16.26), higher stage of CAM (AOR = 2.72), and receiving endoscopic debridement and transcutaneous retrobulbar amphotericin B (AOR = 3.30) had higher odds of mortality. History of taking systemic corticosteroids during COVID-19 was significantly associated with reduced odds of mortality (AOR = 0.16). Generalized Estimating Equations analysis showed that the visual acuity of deceased patients (LogMAR: 3.71, 95% CI: 3.04-4.38) was worse than that of patients who were discharged from the hospital (LogMAR: 2.42, 95% CI: 2.16-2.68) (P < 0.001). CONCLUSIONS: This study highlights significant risk factors for mortality in patients with CAM, such as cigarette smoking, ICU admission, advanced CAM stages, receiving transcutaneous retrobulbar amphotericin B and worser visual acuity. Conversely, a history of systemic corticosteroid use during COVID-19 was linked to reduced mortality. These findings underscore the critical need for early identification and targeted interventions for high-risk CAM patients to improve clinical outcomes.

Lower Eyelid Position Changes Following Müller's Muscle-Conjunctival Resection Blepharoptosis Surgery.

BACKGROUND: Asymmetry of the lower eyelids and a lower position of the lower eyelid on the ptotic side are common issues in patients with upper lid ptosis. Understanding the relationship between upper lid ptosis correction and lower eyelid position will facilitate better treatment strategies for ptosis. OBJECTIVES: The aim of this study was to assess the lower eyelid position before and after Müller's muscle-conjunctival resection (MMCR) in unilateral myogenic ptosis (MP) and aponeurotic ptosis (AP). METHODS: This prospective interventional before-and-after study included adults with blepharoptosis. Measurements were taken before and 6 months after the surgery. RESULTS: A total of 47 patients were included, with 29 having MP and 18 having AP. The mean [standard deviation] ages were 31.55 [5.30] years and 50.11 [6.45] years, respectively. In the MP group, there was a significant association between baseline margin reflex distance 2 (MRD2) and the severity of ptosis (MRD1) (ß = -0.739, P = .004, multivariate regression analysis). After MMCR, significant decreases were observed in MRD2 for both the MP (-0.38 [0.48] mm, P < .001) and AP (-0.39 [0.47] mm, P = .003) groups. The symmetry of MRD2 remained stable at 41.4% in the MP group, while it decreased from 44.4% to 16.7% in the AP group. The baseline MRD2 was the only factor associated with postoperative MRD2 in the MP group. CONCLUSIONS: Patients with MP and AP often exhibit a lower position of the lower eyelid, which typically elevates after posterior upper lid ptosis surgery. In myogenic cases, the severity of preoperative lower eyelid position correlates with the severity of upper lid ptosis and predicts postoperative elevation of the lower lid.

Long-Term Results of Oral Propranolol Treatment Protocol for Periocular Infantile Hemangioma: Should There Be Any Contraindication?

PURPOSE: The authors report long-term results of the oral propranolol treatment protocol for periocular infantile hemangioma regardless of conventional indications. METHODS: This is a retrospective study (2008-2018) on children with propranolol treatment protocol for periocular infantile hemangioma and last follow-up (FU) of ≥4 months after treatment and age of >24 months. After systemic evaluation, it was started with 0.5 and increased by 0.5 every 3 days to reach 2 mg/kg/day. If there was no good response, it would be gradually increased up to 3 mg/kg/day. Tapering (0.5 mg/kg/day every 4 weeks) was started when patients were on treatment for ≥6 months and ≥12 months old and there was no change in the infantile hemangioma size for ≥3 months. Rebound growth was based on the parents' report and would be treated by increasing the dose to at least 2 mg/kg/day for 3 months. FU was either in-person or via social media. Change in periocular infantile hemangioma size on the photos was scored by 3 masked observers (visual analog scale) and presented as excellent (≥50% reduction), good (1%-49%), fair (no change), and failure (enlarged). RESULTS: Forty-three patients were included. Orbital involvement was in 49%, ptosis in 58%, and risk of amblyopia in 63%. Mean treatment, tapering, and FU duration were 37, 13, and 74 months, respectively. Mean age at presentation, start of propranolol treatment protocol, tapering, stop, and last FU were 1.5, 5, 29, 42, and 78 months, respectively. Twenty-seven patients received 2, seven 2.5, and nine 3 mg/kg/day. Mean visual analog scale significantly increased from 43% (FU1) to 92% (last FU) when 97.6% of patients showed an excellent response. The remaining skin lesions were observed in 35%. No side effect was reported. CONCLUSIONS: Long-term results of the propranolol treatment protocol for periocular infantile hemangioma showed an excellent response in 97.6% of patients with no side effects. A residual skin lesion was observed in 1/3 of the patient.

Anaplastic Large Cell Lymphoma With Intraocular or Ocular Adnexal Involvement: A Case Report and Systematic Review.

PURPOSE: To review the existing literature on patients with anaplastic large cell lymphoma (ALCL) affecting the globe and/or ocular adnexa, and to present a report documenting the clinical course of a patient with ALCL that involved their globe and ocular adnexa. METHODS: PubMed, Scopus, and Google scholar were systematically searched for all cases of ALCL involving intraocular or adnexal ocular structures from inception to May 2023. Moreover, a new reported case added to the cases found in searches. RESULTS: The review identified 1680 studies, with 8 meeting inclusion criteria. A total of 9 patients were included with a mean age of 29.7 years (median: 30.0, range: 1.3-48). Primary ALCL was present in 5/9 (55.6%) patients. The most common ophthalmic manifestations included periorbital swelling (5/8), chemosis (5.8), and decreased vision (5/7). Misdiagnoses were initially made in 3 patients, and the lag time to correct diagnosis from 3 weeks to 3 months. CD30 expression was positive in all cases, and 6/9 patients were positive for anaplastic lymphoma kinase, resulting in 6/9 patients being diagnosed with anaplastic lymphoma kinase-positive ALCL. In terms of management modalities, chemotherapy was administered in 8/9 patients, while radiation therapy was utilized in 4/9 patients, and 2 underwent autologous stem cell transplantation. Five (55.6%) patients succumbed to ALCL while 4 (44.4%) were alive and disease-free at the last follow-up. The median times from the initial presentation of ALCL to death, ophthalmic presentation to death, and diagnosis to death were 4.12 months (range: 1.1-168.0), 2.62 months (range: 1.1-144), and 4.00 months (range: 0.10-168), respectively. The median follow-up duration was 21.0 months (range: 1.1-168.0). CONCLUSIONS: ALCL involving the globe and ocular adnexa is a rare and highly malignant tumor that can mimic benign clinical conditions. Early biopsy and aggressive treatment with chemotherapy regimens such as CHOP and radiation therapy may be useful.

Minced Free Fat Graft Versus Pedicle Fat Flap to Efface Orbital Rim Hollow in Lower Blepharoplasty.

BACKGROUND: Lower eyelid fat flap repositioning during transconjunctival lower blepharoplasty (TCLB) is a widely accepted technique for preventing postoperative tear trough deformity. Its drawbacks include retraction, limited volume, transcutaneous fixation, and a complex insertion technique. The minced lower eyelid fat graft was introduced to overcome these drawbacks. OBJECTIVES: The aim of this study was to compare the outcome of preperiosteal pedicle fat flaps with minced free fat graft in TCLB. METHODS: Participants who underwent the pedicle fat flap procedure from April 2019 to April 2020 (Group A) and the minced free fat graft from May 2020 to May 2021 (Group B) with at least 6 months of follow-up were included. Subjective (pain, infraorbital numbness) and objective (chemosis, residual skin wrinkles, hyperpigmentation, tear trough deformity, bumps) postoperative outcomes, satisfaction (visual analogue scale score) at the last follow-up, and reoperation rates were compared. RESULTS: There were 142 participants (94% females) with a mean age of 48.4 years (range: 21-71) and a follow-up of 8.2 months (range: 6-36). There were 73 participants in Group A and 69 in Group B, with no significant differences in age (P = .6), sex (P = .7), or follow-up (P = .3). In addition to TCLB, Groups A and B had simultaneous upper eyelid and eyebrow procedures (53% vs 49%, P = .2), lateral canthal plication (77% vs 83%, P = .4), and pinch skin excision (82% vs 88%, P = .3). Groups A and B did not have significant differences in postoperative numbness (6.8% vs 1.4%, P = .2), chemosis (11% vs 10%, P = 1), skin wrinkles (12.3% vs 8.7%, P = .6), hyperpigmentation (1.4% in both groups), bumps (2.7% vs 7.2%, P = .3), tear trough deformity (0.0% in both groups), satisfaction score (97.7% vs 98.1%, P = .4), or reoperation rate (12.3% vs 5.8%, P = .2). CONCLUSIONS: The desired aim of fat redistribution in TCLB seems to be equally achievable with minced fat graft and pedicle fat flap techniques.

Endoscopic-assisted Orbitotomy for Obliteration of Orbital Arteriovenous Fistula Refractory to Endovascular Techniques.

Orbital arteriovenous fistula is a rare acquired disorder. The coincidence of arteriovenous fistula with lymphaticovenous malformation is even rarer. The optimal treatment, thus, is controversial. Surgical approaches vary widely, with associated pros and cons. The purpose of this case report is to describe an orbital arteriovenous fistula in a 25-year-old man with congenital fronto-orbital lymphaticovenous malformation, refractory to endovascular techniques, which was later successfully ablated by a direct endoscopic-assisted orbital approach.

A Systematic Review on the Role of Antioxidants in Thyroid Eye Disease.

Purpose: To systematically review the role of antioxidants in management of patients with thyroid eye disease (TED). Methods: A literature search of the electronic databases was performed without restrictions on the date of publication till the end of March 2021, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Clinical trials, case-control studies, cohorts, case series, case reports, and experimental (including in vitro) studies in the English language were included. The primary outcome in human studies was improvement in severity, activity scores, and/or quality of life scores. There was a decrease in the level of H2O2-dependent oxidative stress, Hyaluronic acid release, reactive oxygen species, cell proliferation, or antifibrotic/antiproliferative actions in the in vitro studies. Results: Out of 374 initially screened articles, 157 studies were selected, the full texts of 82 were reviewed, and 14 papers were finally included. There were 4 clinical and 10 in vitro studies from 1993 to 2018. While ß-carotene, retinol, Vitamin E, Vitamin C, melatonin, resveratrol, N-acetyl-l-cysteine, and quercetin showed some efficacy in in vitro studies; allopurinol, nicotinamide, pentoxifylline, and selenium (Se) were effective in both clinical and experimental reports. Se was the only recommended antioxidant based on one high-level randomized controlled trial. Conclusion: While different antioxidants could potentially be effective in the management of TED, no strong recommendation for any or combination of antioxidants could be made to be implemented in the daily practice.

Lacrimal Canalicular Bypass Surgery with Autologous Superficial Temporal Artery Graft.

Purpose: To describe superficial temporal artery graft as a new autologous tissue to reconstruct the upper lacrimal drainage system. Methods: We explain the history of a 30-year-old female with upper lacrimal drainage system obstruction, in whom conjunctivodacryocystorhinostomy (CDCR) failed to resolve epiphora. A superficial temporal artery graft was harvested, intubated with Masterka tube, and implanted between the conjunctiva and nasal cavity. Masterka was replaced with a thicker dummy tube 12 weeks postoperatively. The adequacy of the graft was checked with irrigation tests in follow-up visits from 1 to 26 months after the procedure. Results: Superficial temporal artery autograft successfully eliminated epiphora of the patient in whom (CDCR) with Jones tube failed to make her symptom free. Conclusion: Superficial temporal artery autograft as an autogenous tissue with adequate characteristics can be considered in selective patients of upper lacrimal obstruction to reconstruct the lacrimal drainage system.

Long-term Results of Palpebral Fissure Transfer With No Lower Eyelid Spacer in Chronic Progressive External Ophthalmoplegia.

PURPOSE: To evaluate the long-term outcomes of the palpebral fissure transfer (PFT) technique without lower eyelid spacer in patients with chronic progressive external ophthalmoplegia (CPEO). DESIGN: Retrospective interventional case series. METHODS: Consecutive patients with CPEO with PFT surgery (2006-2017) and a minimum follow-up of 24 months were included. The PFT included simultaneous levator resection or frontalis sling (based on the levator function and Bell's phenomenon) and lower eyelid retractor recession without spacer. Primary outcome measures included the change in margin reflex distance 1 (MRD-1), MRD-2, and palpebral fissure height (PFH) in the course of time. Potential predictors of keratopathy were also explored. RESULTS: There were 32 patients (64 eyelids) with the mean age and follow-up of 34.1 years (range 15-56 years) and 37.9 months (range 24-72 months), respectively. Mean MRD-1 significantly increased from -0.9 mm to 3.4 mm in postoperative weeks 1 and 2 and 1.8 mm at the last follow-up. Mean MRD-2 significantly decreased from 5.6 mm to 3.7 mm in postoperative weeks 1 and 2 and 5 mm at the last follow-up. Eyes with frank lower eyelid retraction (MRD-2 >5 mm) gained more reduction in MRD-2 compared with those with no sclera show (-0.9 mm vs -0.3 mm, P < .001). Reoperation was performed in 9 eyelids for under- (n = 5) and overcorrection (n = 4). Persistent keratopathy was observed in 3 eyes (4.5%). CONCLUSION: Lower eyelid retractor recession without spacer yields significant protective corneal coverage at the critical early postoperative period when the risk of keratopathy is highest.

Pulled versus Pushed Monocanalicular Silicone Intubation in Adults with Lacrimal Drainage System Stenosis: A Comparative Case Series.

PURPOSE: To compare the success rate and complications of pulled versus pushed monocanalicular intubation in adults with incomplete lacrimal drainage system obstruction (lacrimal drainage system stenosis). METHODS: Patients with lacrimal drainage system stenosis (Munk grade ≥3), including both nasolacrimal duct (NLD) stenosis and common canalicular stenosis, were recruited in this prospective comparative case series. Patients underwent probing and either Monoka (51 eyes) or Masterka (48 eyes) intubation under general or local anesthesia. Tubes were removed 4-14 weeks after the procedure. Six months after tube removal, Munk grades 0 and 1 were defined as a complete success, Munk grade 2 was defined as a partial success, and Munk grade ≥3 was defined as failure. All complications were recorded. RESULTS: Ninety-nine eyes from 89 patients with lacrimal drainage system stenosis who underwent either Monoka (51 eyes) or Masterka (48 eyes) intubation were included. The mean (SD) age of the patients was 55.4 (12) years in the Monoka group and 53.5 (12.9) in the Masterka group. Groups were matched on demographics. Masterka intubation could not be performed in one eye. Complete and partial successes were observed in 52.9% (27/51) and 17.6% (9/51) of eyes in the Monoka group and 42.6% (20/47) and 12.8% (6/47) of eyes in the Masterka group, respectively (p=0.29). There was a trend toward a higher total success rate in patients with NLD stenosis treated with Monoka 66.7% (26/39) than Masterka 45.5% (15/33) intubation (p=0.07). This trend also existed in patients with common canalicular stenosis (83.3% (10/12) vs. 76.6% (11/14), p=0.75). Age, sex, bilateral involvement, and duration of intubation did not have a significant impact on the success rate. Early tube loss, slit puncta, and temporary superficial punctate keratopathy were observed complications. CONCLUSION: Intubation with the pulled monocanalicular silicone tube was associated with a slightly but not significantly higher success rate in adults with lacrimal drainage system stenosis. Patients with NLD stenosis may achieve better results with pulled silicone tubes.