The continuous rise in orbital subperiosteal abscess incidence in the Iranian pediatric population.

In this study, we aimed to follow up on the surprising increase in the incidence of orbital subperiosteal abscesses (SPA) reported in the Iranian pediatric population in the post-COVID era. Pediatric patients (≤ 18 years old) diagnosed with orbital SPA following acute sinusitis who were hospitalized between October 1st, 2023, and March 31st, 2024 in Farabi Eye Hospital, Tehran, Iran, were included. Demographic, clinical, microbiologic, and radiological characteristics of patients were reviewed. During the 6-month study period, 39 patients were admitted to our tertiary referral hospital. The average age of patients was 7.29 ± 4.13 years and 30 patients (76.92%) were male. The ethmoid sinus was involved in 100% of patients, and SPA involvement was in the medial wall in 27 patients (69.23%). The mean volume of SPA was 1.45 ± 1.77 cm3. Nineteen patients (48.72%) underwent surgical interventions, however, 20 patients (51.28%) received only medical treatment. The best corrected visual acuity of patients increased from 0.63 (0.20 LogMAR) on the first day of admission to 0.84 (0.07 LogMAR) according to the Snellen chart in the first month after treatment. It seems that the outbreak of orbital SPA in the Iranian children population in the post-COVID era is an increasing trend.

Comparative efficacy of probing with or without intubation, and/or inferior turbinate fracture in simple congenital nasolacrimal duct obstruction: a randomized clinical trial.

To compare the success rates of probing with or without monocanalicular intubation, and/or inferior turbinate fracture in resolving simple congenital nasolacrimal duct obstruction (CNLDO). A randomized, double-blind clinical trial was conducted on children aged 12-36 months exhibiting symptoms of epiphora and/or mucous discharge along with a positive fluorescein dye disappearance test (DDT). Patients were randomly assigned to one of the following interventions: (1) probing; (2) probing and monocanalicular intubation; (3) probing and inferior turbinate fracture; (4) probing, inferior turbinate fracture, and monocanalicular intubation. Participants were categorized into two age groups (12-24 months and 24-36 months) and assessed for resolution of CNLDO three months post-surgery. Success was defined as the absence of epiphora or mucopurulent discharge and a negative DDT. Among the 201 participants, 51 underwent probing alone, 53 underwent probing with intubation, 47 underwent probing with turbinate fracture, and 50 underwent probing with turbinate fracture and intubation. No significant differences were observed in age, gender, or laterality of the disease between the groups (Ps > 0.05). While there was no significant difference in success rates among interventions in both age groups (Ps > 0.05), patients aged 24-36 months who underwent interventions involving intubation exhibited a significantly higher success rate compared to those without intubation (93.0% vs. 76.2%; P = 0.018). However, this difference was not observed in patients aged 12-24 months (95.7% vs. 92.9%; P = 0.551). Incorporating interventions such as intubation and/or turbinate fracture alongside conventional probing does not significantly alter the success rate of simple CNLDO resolution in children aged 12-24 months. However, older patients (24-36 months) may derive greater benefits from interventions involving intubation.

Biomechanical changes of the cornea after orbital decompression in thyroid-associated orbitopathy measured by corvis ST.

This study aims to investigate the changes in ocular biomechanical factors in patients with inactive thyroid eye disease (TED) who undergo orbital decompression surgery. This observational prospective study include 46 eyes of 31 patients with inactive TED undergoing orbital decompression at a tertiary university hospital from October 2021 to September 2023. All participants underwent a full ophthalmic examination, and a biomechanical examination was performed using corvis ST at baseline, 1 month, and 3 months postoperatively. The study participants had a mean age of 45 ± 11.6 years, and 58.1% of them were female. The second applanation time (A2T) increased from baseline to postoperative month 1 and continued to increase to postoperative month 3 (P < 0.001). The first applanation velocity (A1V), highest concavity (HC) peak distance, and pachymetry parameters also increased from postoperative month 1 to postoperative month 3 (P = 0.035, P = 0.005, and P = 0.031, respectively). The HC time increased from baseline to postoperative month 3 (P = 0.027). Other changes were statistically insignificant. The P-values were adjusted according to biomechanically corrected intraocular pressure (bIOP). Baseline Hertel significantly influenced A2 time (P < 0.001). Our findings suggest that ocular biomechanical parameters may change following decompression surgery in patients with inactive TED. Specifically, an increase in A2T, A1V, and HC peak distance suggests a decrease in corneal stiffness, although the increased HC time contradicts this. It is recommended to postpone keratorefractive or intraocular lens implantation surgeries until corneal biomechanics stabilize after decompression surgery for optimal results.

Optical coherence tomography angiography in thyroid associated ophthalmopathy: a systematic review.

PURPOSE: To evaluate the evidence for alterations of blood flow, vascular and perfusion densities in the choroid, macula, peripapillary region, and the area surrounding the optic nerve head (ONH) in patients with thyroid-associated ophthalmopathy (TAO) based on changes of OCTA parameters. METHODS: A systematic review of Pubmed, Google Scholar, Scopus, WOS, Cochrane, and Embase databases, including quality assessment of published studies, investigating the alterations of OCTA parameters in TAO patients was conducted. The outcomes of interest comprised changes of perfusion and vascular densities in radial peripapillary capillary (RPC), ONH, superficial and deep retinal layers (SRL and DRL), choriocapillaris (CC) flow, and the extent of the foveal avascular zone (FAZ). RESULTS: From the total of 1253 articles obtained from the databases, the pool of papers was narrowed down to studies published until March 20th, 2024. Lastly, 42 studies were taken into consideration which contained the data regarding the alterations of OCTA parameters including choriocapillary vascular flow, vascular and perfusion densities of retinal microvasculature, SRL, and DRL, changes in macular all grid sessions, changes of foveal, perifoveal and parafoveal densities, macular whole image vessel density (m-wiVD) and FAZ, in addition to alterations of ONH and RPC whole image vessel densities (onh-wiVD and rpc-wiVD) among TAO patients. The correlation of these parameters with visual field-associated parameters, such as Best-corrected visual acuity (BCVA), Visual field mean defect (VF-MD), axial length (AL), P100 amplitude, and latency, was also evaluated among TAO patients. CONCLUSION: The application of OCTA has proven helpful in distinguishing active and inactive TAO patients, as well as differentiation of patients with or without DON, indicating the potential promising role of some OCTA measures for early detection of TAO with high sensitivity and specificity in addition to preventing the irreversible outcomes of TAO. OCTA assessments have also been applied to evaluate the effectiveness of TAO treatment approaches, including systemic corticosteroid therapy and surgical decompression.

Orbital intramuscular hydatid cyst causing compressive optic neuropathy: a case report and literature review.

BACKGROUND: Echinococcosis, commonly known as hydatid disease, is a zoonotic infection resulting from the tapeworm Echinococcus granulosus. The occurrence of hydatid cysts in the orbital region is uncommon, representing less than 1% of all reported hydatid cases. This report details a unique case of an intramuscular hydatid cyst in the orbital region that led to compressive optic neuropathy. CASE PRESENTATION: A 22-year-old male from Kabul, Afghanistan presented with a five-month history of progressive proptosis in his left eye, associated with a gradual decrease in vision over the past three weeks. The left eye exhibited upward globe dystopia, ocular motility limitation, mild conjunctival injection, and chemosis. Diagnosis was achieved through imaging and histopathological examination. Treatment involves surgical removal of the cyst and prolonged albendazole therapy. The postoperative course showed significant improvement in the patient's condition and restoration of his vision. CONCLUSIONS: Despite its rarity, this case underscores the importance of awareness and knowledge of hydatid disease among physicians, especially those working in endemic areas. It emphasizes the importance of including hydatid disease in the differential diagnosis of orbital masses, particularly in endemic regions.

Superficial ocular vascular changes after orbital decompression in patients with thyroid ophthalmopathy measured by anterior segment OCT angiography; an observational study.

Thyroid eye disease (TED) is a common ophthalmologic manifestation of thyroid dysfunction. Despite various imaging techniques available, there hasn't been a widely adopted method for assessing the anterior segment vasculature in TED patients. Our study aimed to evaluate alterations in ocular surface circulation following orbital decompression surgery in TED patients and investigate factors influencing these changes. Using anterior segment optical coherence tomography-angiography (AS-OCTA), we measured ocular surface vascularity features, including vessel density (VD), vessel diameter index (VDI), and vessel length density (VLD), both before and after decompression surgery, alongside standard ophthalmic examinations. Our AS-OCTA analysis revealed a significant decrease in most of the temporal vasculature measurements six weeks post-surgery (p < 0.05). However, differences in the nasal region were not statistically significant. These findings indicate notable changes in ocular surface circulation following orbital decompression in TED patients, which may have implications for intraocular pressure (IOP) control and ocular surface symptoms management. AS-OCTA holds promise as a tool for evaluating the effectiveness of decompression surgery and assessing the need for further interventions.

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.

Orbital histiocytosis; From A to Z.

PURPOSE: Histiocytosis is one of the most challenging diseases in medical practice. Because of the broad spectrum of clinical manifestations, systemic involvements, unknown etiology, and complex management, different types of histiocytosis are still a big question mark for us. Orbital histiocytosis is characterized by the abnormal proliferation of histiocytes in orbital tissues. It could affect the orbit, eyelid, conjunctiva, and uveal tract. Orbital histiocytosis can cause limited eye movement, proptosis, decreased visual acuity, and epiphora. In this study, we review the novel findings regarding the pathophysiology, diagnosis, and treatment of different types of histiocytosis, focusing on their orbital manifestations. METHOD: This review was performed based on a search of the PubMed, Scopus, and Embase databases or relevant published papers regarding orbital histiocytosis on October 9th, 2023. No time restriction was proposed, and articles were excluded if they were not referenced in English. RESULTS: 391 articles were screened, most of them being case reports. The pathophysiology of histiocytosis is still unclear. However, different mutations are found to be prevalent in most of the patients. The diagnostic path can be different based on various factors such as age, lesion site, type of histiocytosis, and the stage of the disease. Some modalities, such as corticosteroids and surgery, are used widely for treatment. On the other hand, based on some specific etiological factors for each type, alternative treatments have been proposed. CONCLUSION: Significant progress has been made in the detection of somatic molecular changes. Many case studies describe various disease patterns influencing the biological perspectives on different types of histiocytosis. It is necessary to continue investigating and clustering data from a broad range of patients with histiocytosis in children and adults to define the best ways to diagnose and treat these patients.

Prediction of substantial closed-globe injuries in orbital wall fractures.

PURPOSE: To determine risk factors for substantial closed-globe injuries in orbital fractures (SCGI) and to develop the best multivariate model for the prediction of SCGI. METHODS: A retrospective study was performed on patients diagnosed with orbital fractures at Farabi Hospital between 2016 and 2022. Patients with a comprehensive ophthalmologic examination and orbital CT scan were included. Predictive signs or imaging findings for SCGI were identified by logistic regression (LR) analysis. Support vector machine (SVM), random forest regression (RFR), and extreme gradient boosting (XGBoost) were also trained using a fivefold cross-validation method. RESULTS: A total of 415 eyes from 403 patients were included. Factors associated with an increased risk of SCGI were reduced uncorrected visual acuity (UCVA), increased difference between UCVA of the traumatic eye from the contralateral eye, older age, male sex, grade of periorbital soft tissue trauma, trauma in the occupational setting, conjunctival hemorrhage, extraocular movement restriction, number of fractured walls, presence of medial wall fracture, size of fracture, intraorbital emphysema and retrobulbar hemorrhage. The area under the curve of the receiver operating characteristic for LR, SVM, RFR, and XGBoost for the prediction of SCGI was 57.2%, 68.8%, 63.7%, and 73.1%, respectively. CONCLUSIONS: Clinical and radiographic findings could be utilized to efficiently predict SCGI. XGBoost outperforms the logistic regression model in the prediction of SCGI and could be incorporated into clinical practice.

Pediatric orbital subperiosteal abscess outbreak in Iran: characteristics and causes.

PURPOSE: To evaluate demographics, characteristics, and management of pediatric patients with subperiosteal abscesses (SPA) secondary to orbital cellulitis and discuss the etiology of a dramatic rise in SPA. METHODS: Data were gathered by retrospective chart review of patients admitted to a tertiary referral eye hospital (Farabi Eye Hospital) diagnosed with orbital cellulitis with subperiosteal abscess from October 2022 to March 2023 (six months). Data on demographic information, clinical examination, radiographic evidence of sinusitis, orbital cellulitis, SPA, surgical and non-surgical management taken, isolated bacteria, and duration of hospital stay were gathered. RESULTS: 24 patients were admitted during these six months, with a diagnosis of orbital SPA secondary to paranasal sinusitis, confirmed by an orbital Computed Tomography (CT) scan. The age range was 11 months to 16 years. 75% of patients were male. All patients had a history of flu-like illness before developing orbital cellulitis. All patients had concurrent sinusitis, and 18 underwent initial surgical abscess drainage. The ethmoid sinus was the most involved, and most patients had a medially located SPA. Abscess volume ranged from 0.78 to 7.81 cm3 (mean: 3.52 cm3). One patient had concurrent central retinal artery occlusion due to orbital cellulitis. CONCLUSIONS: In this study, we report a dramatic increase in the incidence of SPA referred to our hospital. Larger abscess volumes and an increased number of cases that needed initial surgical drainage are also of note. An influenza outbreak in the autumn and winter, undiagnosed Corona Virus Disease 2019 (COVID-19) infection, increased antimicrobial resistance due to excessive off-label use of antibiotics during the COVID-19 pandemic, and more virulent bacterial infections are the most probable hypotheses to justify this observation.

Videographic analysis of blink dynamics in patients with chronic progressive external ophthalmoplegia, myogenic ptosis, and facial nerve palsy using smartphone camera: A comparative analysis.

Background and Aims: Congenital myogenic ptosis (CMP), chronic progressive external ophthalmoplegia (CPEO), and facial nerve palsy (FNP) are among the disorders which can seriously affect the blink dynamics of patients. Smartphone videography is a simple, convenient, and inexpensive way to capture eyelid movement. This study has measured and compared a variety of blink dynamics in these patients compared to healthy controls using 2-dimensional smartphone videography to enhance the utility of this method in both clinical and research settings. Methods: A total of 30 adult participants with a complaint of impaired eyelid movements including 10 with CMP, 10 with CPEO, and 10 with unilateral FNP, as well as 10 healthy controls were recruited. Using a smartphone camera with a resolution of 240 frames per second in 720 p, various blink dynamics were measured. Results: All case groups had significantly lower values of peak and average closing velocities, average opening velocity, and palpebral aperture and significantly higher values of eyelid closing duration, compared to controls. FNP participants also had significantly lower values in the full blink rate and peak opening velocity (POV) measures, and CPEO patients showed significantly lower values in the POV. Other measures were not statistically significantly different compared to healthy controls. Conclusion: Our results indicated that all patients with CMP, FNP, and CPEO had different blinking dynamics compared to healthy controls, which is consistent with previous studies. Smartphone videography has achieved sufficient resolution and frame-rate to provide valuable information and anatomic details for clinical and research purposes. Further studies could utilize smartphone videography for further investigation and confirmation of the methodology in various conditions.

Orbital histiocytosis and fibrohistiocytosis: the clinicopathological characteristics of 117 patients, over a decade of experience.

PURPOSE: To describe the clinicopathological features of a large cohort of patients with orbital histiocytoses and fibrohistiocytosis, such as Langerhans cell histiocytosis (LCH) and non-LCH disorders, and correlate patients' clinical characteristics with their pathological diagnosis. METHODS: In this retrospective study, medical records of patients presenting to Farabi Eye Hospital, a tertiary eye care center in Tehran, Iran, from 2010 until 2022, were reviewed. Patients' demographics, chief complaint, location and laterality of the tumor, best-corrected visual acuity, presence of bone erosion on imaging, and their pathological diagnosis were retrieved. Excisional biopsy was performed and evaluated through light microscopy and immunohistochemistry study for their respective markers, including CD1a, CD68, CD207, and S100. RESULTS: A total of 117 patients with 11 pathological subtypes of histiocytoses and fibrohistiocyosis were identified, with 56.4% male and 43.6% female patients. The mean age at presentation was 23.4 years (range 1.5 months-73 years). Swelling and palpable mass were the most common chief complaints. LCH was the most common pathology (32.5%), followed by juvenile xanthogranuloma (26.5%) and adult xanthogranuloma (21.4%). Age, lesion location, and bone erosion had a statistically significant difference among the various diagnosed subtypes. CONCLUSIONS: Histiocytoses and fibrohistiocytosis are diverse and rare disorders potentially involving multiple organ systems. Ophthalmic manifestations of these diseases are even more uncommon. We reviewed their orbital presentation along with their respective histopathological findings. Our results also suggested that an orbital CT scan can be of diagnostic value to discriminate LCH from other histiocytic pathologies.

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.

Unusual orbital mucormycosis due to pecking injury: clinical characteristics and outcomes of four immunocompetent pediatric patients.

Mucormycosis is a serious fungal infection caused by fungi in the order of Mucorales. Orbital mucormycosis occurs more frequently in rhino-orbital, sino-orbital, and rhino-orbito-cerebral forms of the disease, while isolated orbital mucormycosis is much less common. Herein, we present four cases of immunocompetent children who developed primary cutaneous mucormycosis, which subsequently invaded and progressed to orbital mucormycosis following direct traumatic injury caused by pecking from Acridotheres tristis (Common Myna). Given the low prevalence of orbital mucormycosis in healthy children, an unknown source of infection and delayed diagnosis followed by late therapeutic interventions could result in life-threatening conditions and serious sequelae.

Corneal biophysical changes after upper eyelid blepharoplasty and ptosis surgery: a review.

Upper eyelid surgeries, such as blepharoplasty and ptosis correction, are commonly performed procedures worldwide. This review examines the effects of these surgeries on ocular properties and visual function. A search of the PubMed and Google Scholar databases was conducted to identify relevant articles published after 2000. The results demonstrate that the ocular and adnexal organs function as a unified visual system, with changes in one component affecting the functions of others. Eyelid surgery can alter ocular properties and functions by modifying retinal lighting and ocular optics. These alterations can affect intraocular pressure estimation, corneal curvature, corneal epithelial thickness, refractive power of the cornea, and intraocular lens calculation. Additionally, eyelid surgery can exacerbate dry eye symptoms and impact contrast sensitivity, which is a significant factor in visual quality. Therefore, understanding these interactions is crucial before performing eyelid surgery and during follow-up. This review summarizes recent literature on the effects of upper eyelid surgery on corneal properties and visual function, emphasizing the importance of considering these factors when planning or undergoing such procedures.

COVID-19 associated rhino-orbito-cerebral mucormycosis, risk factors and outcome predictors; a multicentric study.

BACKGROUND: Since the onset of the Covid-19 pandemic, an increase in mucormycosis cases has been observed in many countries, including Iran. However, the role of covid-19 and associated risk factors have not been thoroughly investigated. OBJECTIVE: This study is designed to identify epidemiologic characteristics, risk factors, and outcome predictors of Covid-19-Associated Rhino-Orbito-Cerebral Mucormycosis (C-ROCM). METHODS: Data of pathology proven Covid Associated ROCM cases were retrospectively obtained from 7 tertiary care centers throughout Iran from February 20, 2021, to July 22, 2021. Univariate and multivariate analyses were performed using binary logistic regression to assess the effects of various factors on the outcome. RESULTS: A total of 132 patients with C-ROCM were included in the study. The mean age of patients was 61.6 ± 13.9 (60.6% male). In 12 patients (9.1%), both eyes were involved. Diabetes was the most common comorbidity (94.7%). The mortality rate was 9.1%, higher in males (12.5%) than females (3.8%). Severe vision impairment was seen in 58 patients (43.9%). Main factors that had a negative impact on the outcome in the univariate analysis include older age (P < 0.001), higher steroid dosage (P < 0.001), higher HbA1c level (P < 0.001), Covid-19 severity (P < 0.001), and brain involvement (P < 0.001). However, in the multivariate analysis, the effects of age (P = 0.062), steroid dosage (P = 0.226), and Covid-19 intensity (P = 0.084) decreased, and the difference was no longer statistically significant. CRAO was a predictor of mortality in the univariate analysis (P = 0.008, OR = 4.50), but in the multivariate analysis, this effect decreased and was no longer significant (P = 0.125). CONCLUSION: The risk of C-ROCM and its complications may increase in patients with more severe Covid-19, steroid over-prescription, ICU admission due to Covid-19, and poor glycemic control during and after Covid-19 treatment.

Isolated schwannoma originating from the infraorbital nerve: A case report.

As a benign isolated and encapsulated tumor originating from the nerve sheaths, schwannomas rarely appear on the cranial nerves, among which infraorbital nerve schwannomas are highly uncommon. We report a case of isolated infraorbital nerve schwannoma in a 58-year-old male patient with a clinical manifestation of proptosis in the affected eye.

Mycophenolate Mofetil (CellCept®) in Combination With Low Dose Prednisolone in Moderate to Severe Graves' Orbitopathy.

Although corticosteroids are currently the first-choice drug for thyroid eye disease (TED), in 20-30% of cases, patients show poor or non-existent responses, and when the drug is withdrawn, 10-20% of patients relapse. Thus, in this study, we aimed to investigate the efficacy of the combined use of mycophenolate mofetil (CellCept®) and low dose oral prednisolone in patients with moderate to severe Graves' orbitopathy (GO). For the first time, we investigated the relationship between TED-related parameters and proptosis reduction. In a prospective, non-randomized, interventional case series, 242 patients with moderate-to-severe GO were, assigned to receive oral prednisolone (5 mg/ d) and mycophenolate mofetil (CellCept®) (one 500 mg tablet twice per day according to the therapeutic response). The patients were monitored regularly during the 3rd, 6th, 12th, and 18th month of treatment. The main outcome measures were the clinical activity score (CAS), intraocular pressure (IOP), diplopia, proptosis and visual acuity. We also assessed the relationship between the main outcomes with proptosis changes and time to improvement (months). Adverse effects were recorded during each visit. The clinical response rate increased from 67.7% on the third month to 89.2% on the sixth month, and 94.2% on the 12th month. This therapeutic response continued until the 18th month of follow-up. The CAS responses [disease inactivation (CAS <3)] improved during our study: 70.6% on the third month, 90.0% on the sixth month, and 92.5% at 12th month. These conditions continued until the 18th month of follow-up. Proptosis improvement was 52% on the third month, 71% on the sixth month, 83% on the 12th month, and 87.1% on the 18th month. Changes in IOP and visual acuity were not significant (P = 0.568 and 0.668, respectively). The patient showed significant improvement in the Gorman score. A Shorter duration of treatment was seen in patients with earlier onset of intervention, younger age, and lack of all extraocular muscle (EOM) enlargement on computed tomography (CT) scan (p < 0.05). In addition, a better response (more reduction) in proptosis was related to: younger age at disease, earlier treatment intervention (less interval from the time the diagnosis of moderate-to-severe GO was made until medication initiation), shorter treatment time (less time to improvement), less IOP, lack of EOM enlargement on CT scan, and lack of diplopia (P < 0.05). Adverse events occurred in six patients. Findings show that mycophenolate mofetil (CellCept®) plus low-dose prednisolone can be introduced as a new optimal dosing regimen in GO due to its better effect on chronic complications such as proptosis and diplopia.