Clinical Outcome and Technical Nuances After Resection of Orbital Cavernous Venous Malformations-A Single-Center Experience.

BACKGROUND: Cavernous venous malformations (CVMs) represent the most common benign intraorbital lesions. Enlarging or symptomatic CVMs (progressive proptosis or visual disturbances) are treated by surgical resection. For this, a variety of different surgical approaches have been described. The aim of this study was to present a contemporary series of orbital CVMs treated via open microsurgical approaches. METHODS: In this study, patients who underwent resection of orbital CVMs between 2002 and 2019 were included. Presenting symptoms were noted and neuro-ophthalmologic examinations performed pre- and postoperatively. For surgical resection, the location of the orbital CVM and its relation to the orbital anatomy led to decision-making for appropriate approaches. A comparison between anatomical location and surgical outcome was performed. RESULTS: Overall, 35 patients with orbital CVMs were included. Most common presenting symptoms were progressive proptosis (43%) and visual disturbances (34%). Most common location was the lateral quadrant (37%) followed by the superior quadrant (20%). A subfrontal craniotomy was performed in 40% of cases followed by a supraorbital craniotomy including the orbital rim in 34% of cases. For surgical excision, a cryo-probe was used in 30 patients, and complete resection was feasible in all cases. Location of a CVM within the superior quadrant was associated with improved postoperative recovery of visual acuity. No differences for clinical outcomes were observed depending on the surgical approach. CONCLUSIONS: Resection of orbital CVMs is indicated in patients with visual disturbances or progressive proptosis. In these, microsurgical approaches can be used with minimal morbidity for complete removal of these well-circumscribed lesions.

Unilateral periorbital swelling in children: avoid delays in diagnosis.

A 10-year-old child had painful periorbital swelling in the left eye. It was diagnosed as preseptal cellulitis and treated with oral antibiotics. Three days later, the ocular condition worsened so the child was referred for further management. On examination, the child had a temperature of 102 °F. Ocular examination revealed proptosis, restricted ocular movements and a relative afferent pupillary defect in the left eye. Ocular examination of the right eye was normal. There was a history of recurrent episodes of cold in the past. CT scan orbit and sinuses revealed signs of orbital cellulitis with sinusitis on the left side. The child was treated with parenteral antibiotics and endoscopic sinus surgery. A child presenting with unilateral periorbital swelling needs to be thoroughly evaluated. It is important to differentiate orbital cellulitis from preseptal cellulitis. Orbital cellulitis is an emergency and delay in diagnosis can lead to vision and life-threatening intracranial complications.

Invasive fungal disease misdiagnosed as tumour in association with orbital apex syndrome.

Invasive sino-orbital aspergillosis is a rare cause of orbital apex syndrome (OAS) in immunocompetent patients and often misdiagnosed as tumour because of its aggressive nature and invasive patterns. We report a 23-year-old immunocompetent man presenting with painful progressive loss of vision, ophthalmoplegia and proptosis of the right eye suggestive of OAS. MRI with gadolinium contrast showed an enhancing heterogeneous mass filling the paranasal sinuses, extraconal space and extending up to the right orbital apex. A functional endoscopic biopsy reported as invasive sino-orbital aspergillosis. He was started on intravenous voriconazole and maximal surgical debridement was done. He gradually regained his vision to 20/30 in the right eye. A review of literature reported several such cases which were managed medically or surgically but with poor visual recovery. This case highlights the need for awareness among clinicians for early diagnosis and treatment to prevent vision loss and better survival.

Quantitative analysis of extraocular muscle volume and exophthalmos reduction after radiation therapy to treat Graves' ophthalmopathy: A pilot study.

PURPOSE: The aim of this study was to provide radiological information on the inherent response of Graves' ophthalmopathy after radiation therapy. METHODS: Quantitative analysis of extraocular muscle volume was performed on 96 involved extraocular muscles in a total of 16 patients. A total of 48 computed tomography images were analyzed. Exophthalmos was also measured. The percentage reductions in extraocular muscle volume and exophthalmos length were determined and compared to the pre-radiation therapy values at 6-, 12-, and 24-month follow-up. RESULTS: The median follow-up time was 21.5 months (range: 7.2-29.4 months). The mean reduction in relative tumor volume compared to the pre-radiation therapy extraocular muscle volume was 46.1% (range: 33.3%-58.8%). The mean relative extraocular muscle volumes were 71.5% at 6 months, 59.2% at 12 months, and 54.3% at 24 months after radiation therapy. The volume of the involved extraocular muscles decreased rapidly within the first 12 months of follow-up. The mean pre-radiation therapy length of exophthalmos was 21.7 mm (range: 17.6-26.1 mm). The mean percentages of exophthalmos length by comparison with the pre-radiation therapy length were 96.7% at 6 months, 92.3% at 12 months, and 88.5% at 24 months after radiation therapy. Exophthalmos decreased slowly and steadily during the follow-up period. CONCLUSION: Quantitative volumetric analysis of the pattern of extraocular muscle volume reduction and exophthalmos length reduction in response to radiation therapy will allow clinicians to better understand the effect of radiotherapy on Graves' ophthalmopathy.

A Prospective, Randomized, Double-blind, Placebo-controlled Study of Orbital Radiotherapy for Graves' Ophthalmopathy.

CONTEXT: Although widely used for more than 85 years, the efficacy of radiotherapy for Graves' ophthalmopathy (GO) has not been established convincingly. OBJECTIVE: To evaluate the efficacy of radiotherapy for GO. DESIGN: Prospective, randomized, internally controlled, double-blind clinical trial in a tertiary care academic medical center. PARTICIPANTS: The patients were ethnically diverse males and females over age 30 seen in a referral practice. The patients had moderate, symptomatic Graves' ophthalmopathy (mean clinical activity score, 6.2) but no optic neuropathy, diabetes, recent steroid treatment, previous decompression, or muscle surgery. Forty-two of 53 consecutive patients were enrolled after giving informed consent and fulfilling study entry criteria. Eleven eligible patients declined to participate because of inconvenience, desire for alternative therapy, or concern about radiation. INTERVENTION: One randomly selected orbit was treated with 20 Gy of external beam therapy; sham therapy was given to the other side. Six months later, the therapies were reversed. MAIN OUTCOME MEASURES: Every 3 months for 1 year, we measured the volume of extraocular muscle and fat, proptosis, range of extraocular muscle motion, area of diplopia fields, and lid fissure width. Effective treatment for GO will modify one or more of these parameters. RESULTS: No clinically or statistically significant difference between the treated and untreated orbit was observed in any of the main outcome measures at 6 months. At 12 months, muscle volume and proptosis improved slightly more in the orbit that was treated first. CONCLUSIONS: In this group of patients, representative of those for whom radiotherapy is frequently recommended, we were unable to demonstrate any beneficial therapeutic effect. The slight improvement noted in both orbits at 12 months may be the result of natural remission or of radiotherapy, but the changes are of marginal clinical significance.

A novel FAM20C mutation causes a rare form of neonatal lethal Raine syndrome.

Raine syndrome is a rare, autosomal recessive, osteosclerotic bone dysplasia due to pathogenic variants in FAM20C. The clinical phenotype is characterized by generalized osteosclerosis affecting all bones, cerebral calcifications, and craniofacial dysmorphism. Most cases present during the neonatal period with early lethality due to pulmonary hypoplasia and respiratory compromise while only few affected individuals have been reported to survive into adulthood. FAM20C is a ubiquitously expressed protein kinase that contains five functional domains including a catalytic domain, a binding pocket for FAM20A and three distinct N-glycosylation sites. We report a newborn infant with a history of prenatal onset fractures, generalized osteosclerosis, and craniofacial dysmorphism and early lethality. The clinical presentation was highly suggestive of Raine syndrome. A homozygous, novel missense variant in exon 5 of FAM20C (c.1007T>G; p.Met336Arg) was identified by targeted Sanger sequencing. Following in silico analysis and mapping of the variant on a three-dimensional (3D) model of FAM20C it is predicted to be deleterious and to affect N-glycosylation, protein folding, and subsequent secretion of FAM20C. In addition, we reviewed all published FAM20C mutations and observed that most pathogenic variants affect functional regions within the protein establishing evidence for an emerging genotype-phenotype correlation.

A novel FAM20C mutation causing hypophosphatemic osteomalacia with osteosclerosis (mild Raine syndrome) in an elderly man with spontaneous osteonecrosis of the knee.

Raine syndrome is characterized by FGF23-mediated hypophosphatemic osteomalacia with osteosclerosis caused by mutations in the FAM20C gene. We report a case of a 72-year-old man who presented with rapid progressive spontaneous osteonecrosis of the knee (SONK). A full osteologic assessment including dual energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT), and serum analyses revealed a high bone mass in the lumbar spine and hip (DXA T-score + 7.5 and + 4.7/+4.2) with increased bone microstructural parameters in the distal radius and tibia (BV/TV 127%, 140% of the age-matched mean, respectively), as well as a low bone turnover state. Phosphate levels were low due to renal phosphate wasting and high FGF23 levels (126.5 pg/ml, reference range 23.2-95.4 pg/ml). Using gene panel sequencing, we identified a novel FAM20C heterozygous missense mutation in combination with a homozygous duplication that potentially alters splicing. Taken together, this is the first case of mild Raine syndrome with spontaneous osteonecrosis of the knee, phosphate wasting, and a pronounced trabecular high bone mass phenotype.

A comparative analysis of piezosurgery and oscillating saw for balanced orbital decompression.

Introduction: Different minimally invasive surgical approaches to the orbit allow individualized bone resection to reduce proptosis and decompress the optic nerve in patients with Graves' orbitopathy (GO). This study aims to compare piezosurgery to an oscillating saw used to resect bone from the lateral orbital wall. Methods: In a retrospective study, we analyzed balanced orbital decompressions performed on 174 patients (318 cases) with GO. An oscillating saw was used in 165 cases (saw group) and piezosurgery in 153 cases (piezo group). Peri- and postoperative complications, reduction of proptosis, new onset of diplopia and improvement of visual acuity in cases of pre-operative optic nerve compression were analyzed. Results: We observed no significant differences in the surgical outcome between the two groups. Proptosis reduction was 4.6 mm in the saw group (p < 0.01) and 5.3 mm in the piezo group (p < 0.01). Intraoperative handling of the piezosurgery device was judged superior to the oscillating saw, due to soft tissue conservation and favourable cutting properties. Duration of the surgery did not differ between the groups. No serious adverse events were recorded in both groups. Conclusion: The application of piezosurgery in orbital decompression is more suitable than an oscillation saw due to superior cutting properties such as less damage to surrounding soft tissue or a thinner cutting grove.

Teprotumumab, an insulin-like growth factor-1 receptor antagonist antibody, in the treatment of active thyroid eye disease: a focus on proptosis.

Thyroid eye disease is a disabling autoimmune disease associated with orbital inflammation and tissue remodeling which can result in significant proptosis, leading to visual alterations and is potentially sight threatening. Current evidence indicates that autoantibodies to the insulin-like growth factor 1 receptor (IGF-1R), along with the thyroid-stimulating hormone receptor (TSHR), mediate the pathogenesis in susceptible individuals. Teprotumumab, a monoclonal IGF-1R antagonist, has demonstrated previously in a 24 week, randomized, controlled trial to produce significant changes in composite outcomes of proptosis and clinical activity score as compared with placebo. Further examination of the proptosis results reported here, indicate that the proptosis outcome (≥ 2 mm reduction) was met in 71.4% of the teprotumumab-treated patients as compared with 20% of the placebo-treated patients (p < 0.001). Additionally, the proptosis benefit was observed early in the trial (study week 6), and all individual patients demonstrated some benefit at week 24. Improvement was noted among smokers, non-smokers, men and women, and particularly those with higher levels of proptosis at baseline. The level of proptosis reduction with teprotumumab reported here is similar to that seen with decompression surgery. If these results are confirmed in the ongoing Phase 3 trial, teprotumumab will offer an alternative to surgery and its associated complications.

Clinical pattern of Retinoblastoma in Pakistani population: Review of 403 eyes in 295 patients.

OBJECTIVE: To document clinical pattern of retinoblastoma in Pakistani population. METHODS: This retrospective study, which was conducted at Department of Ophthalmology, Dow University of Health Sciences, Karachi, reviewed clinical records of patients with retinoblastoma from 1997 to 2012. Staging of disease was done by referring to retinal diagrams, RetCam images, and first magnetic resonance imaging. Ophthalmic notes, imaging reports and histopathology reports of enucleated eyes established optic nerve involvement. SPSS 21 was used for statistical analysis. RESULTS: Clinical records of 295 patients with retinoblastoma in 403 eyes were reviewed, and male to female ratio was 1.3:1. Retinoblastoma was bilateral in 106(35.93%) patients, while 118(40%) patients had hereditary pattern. Mean age at presentation was 35.98+27.63 months, while mean follow-up was 3±2 months. Leucokoria was the most common presenting feature 173(58.64%) followed by proptosis 72(24.41%). Optic nerve involvement was seen on magnetic resonance imaging or histopathology in 81(20.10%) eyes. Distant metastasis was noted in 32(10.85%) patients on first presentation. Chemotherapy with or without adjuvant treatment was given to 238(80.68%) patients. Enucleation and exentration were performed in 164(40.69%) and 12(2.98%) eyes, respectively. CONCLUSIONS: Most common presenting symptom was leucokoria followed by proptosis. Hereditary retinoblastoma was frequently seen in Pakistani children. .

A Simple Quantitative Measure of Orbital Compliance.

PURPOSE: This study evaluates the reliability of a frequently used subjective measurement of orbital compliance (0-3 scale) and describes a simple, quantitative measure with excellent intra- and interrater reliability. METHODS: Two examiners performed both measurements on 100 orbits (50 consecutive patients) from the office of 1 oculoplastics surgeon. Each measurement was obtained at 2 different time points, 10 minutes apart. For the subjective measurement, the patient was asked to close their eyes, and the globe was displaced posteriorly with digital pressure until moderate resistance was felt. This was graded on a 0 to 3 scale. For the quantitative measurement (millimeter scale), the difference in axial displacement was measured using a Hertel exophthalmometer. RESULTS: The subjective measurement (scale, 0-3) showed excellent test-retest reliability (average, 0.901) for both examiners at both time points and good interobserver reliability (average, 0.677). The quantitative measurement (millimeter scale) showed excellent test-retest reliability (average, 0.848) and very good interobserver reliability (average, 0.756). CONCLUSION: This study shows that while both methods have both excellent test-retest reliability, the interobserver reliability is slightly higher with the quantitative measurement. This suggests that the described measurement of orbital compliance is both a reasonable alternative and possibly more accurate measurement without the steep learning curve.

A new surgical technique for excision of orbital cavernous hemangioma: a 15-year experience.

PURPOSE: To present a new surgical technique for excision of orbital cavernous hemangiomas (CHs). METHODS: This retrospective case series study included patients with orbital CH who were operated from 2001 to 2016 at our referral center. Epidemiologic data, symptoms, signs, and images were reviewed from patients' files with at least one year of follow-up. Surgical results and complications were documented. We used the "index finger dissection" technique without grasping the tumor for release of adhesions and its removal. RESULTS: We included 60 patients with orbital CH consisting of 36 (60%) female and 24 (40%) male patients with mean age of 40 ± 12.1 (range 9-66) years. The main complaint was proptosis with average size of 5.3 ± 2 millimeters. The surgical approach was lateral orbitotomy in 49 (81.7%) patients, medial transcutaneous in seven (11.7%) patients, inferior transconjunctival in three (5%) patients, and simultaneous lateral and medial orbitotomy in one (1.6%) patient. All tumors were removed intact; complications included ptosis in one subject, lower lid retraction in one case, and diplopia in two patients, all of which improved before 2 months. No optic nerve damage occurred. CONCLUSION: The "index finger dissection" technique without grasping the tumor for excision of orbital CH, via any external approach to the tumor, is a safe technique with minimal complications.

A Rare Eyeball Luxation After Cranioplasty and a Four-Year Follow-Up.

A rare patient of reducible eyeball luxation after cranioplasty in a child Crouzon syndrome was reported. To remedy the patient's chronic intracranial hypertension and brachycephaly, orbitofrontal advancement and cranial vault remodeling were carried out. About 25 days of postoperation, an acute eyeball luxation was observed, with the presence of a subcutaneous accumulation of liquid in the bilateral temporal regions. The dislocated eyeballs were brought back by applying gentle manual pressure. The patient received a conservative treatment without a tarsorrhaphy. The dislocation recurrence never occurred again. In a 4-year follow-up, it was shown that the child's vision was normal and proptosis was improved by series craniofacial reconstructions.

Preoperative clinical features of reactivated of Graves' orbitopathy after orbital decompression.

PurposeTo investigate the incidence and preoperative clinical features of reactivated Graves' orbitopathy (GO) after orbital decompression.MethodsThis study included patients with GO who underwent orbital decompression for disfiguring proptosis and not compressive optic neuropathy and received postoperative follow-up care for more than 12 months. Patients who experienced active inflammatory signs within 6 months of decompression were excluded from analysis. The demographic characteristics, ophthalmic manifestations, and biochemical parameters of the patients were analyzed for association with reactivation of GO by logistic regression analysis.ResultsOut of the 92 patients included in this study, seven (7.6%) experienced reactivation of GO after orbital decompression. The mean time interval between surgery and reactivation of GO was 36.3±14.3 weeks. Univariate logistic regression analysis identified age, existing smoking habits, and modified NOSPECS and Gorman scores as significant factors for the reactivation of GO. The results of multivariate logistic regression analysis revealed that smoking and modified NOSPECS and Gorman scores were associated with the reactivation of GO.ConclusionsQuitting smoking is important for the prevention of reactivation of GO after orbital decompression. Patients with severe symptoms, especially those with restrictive myopathy, should be carefully monitored for reactivation of GO after orbital decompression.

Non lethal Raine syndrome and differential diagnosis.

Raine syndrome is a rare autosomal recessive bone dysplasia characterized by characteristic facial features with exophthalmos and generalized osteosclerosis. Amelogenesis imperfecta, hearing loss, seizures, and intracerebral calcification are apparent in some affected individuals. Originally, Raine syndrome was originally reported as a lethal syndrome. However, recently a milder phenotype, compatible with life, has been described. Biallelic variants inFAM20C, encoding aGolgi casein kinase involved in biomineralisation, have been identified in affected individuals. We report here a consanguineous Moroccan family with two affected siblingsa girl aged 18 and a boy of 15years. Clinical features, including learning disability, seizures and amelogenesis imperfecta, initially suggested a diagnosis of Kohlschutter-Tonz syndrome. However,a novel homozygous FAM20Cvariantc.676T > A, p.(Trp226Arg) was identified in the affected siblings. Our report reinforces that Raine syndrome is compatible with life, and that mild hypophosphatemia and amelogenesis imperfecta are key features of the attenuated form.

Efficacy of combined orbital radiation and systemic steroids in the management of Graves' orbitopathy.

PURPOSE: To compare the efficacy and safety of combination therapy with orbital irradiation and systemic steroids versus steroid monotherapy in the management of active Graves' orbitopathy (GO). METHODS: The clinical charts of 127 patients with active inflammation due to GO who received intravenous steroid pulse therapy as a first-line treatment with or without orbital radiotherapy between 2010 and 2014 were reviewed. Patients were divided into two treatment groups: 1) combined orbital radiotherapy and steroid pulse therapy (SRT group) and 2) steroid pulse therapy only (ST group). Primary outcome measures included clinical activity score (CAS); NOSPECS classification; ocular motility impairment; and exophthalmos at 1, 3, 6, and 12 months after treatment. The secondary outcome measure was the change in orbital, extraocular muscle (EOM), and fat volume after treatment measured by orbit computed tomography. RESULTS: Sixty-eight patients were included in the SRT group, and 59 patients were in the ST group. In both treatments, CAS and NOSPECS were significantly reduced. In the comparison of the degree of change from baseline between the groups, the SRT group demonstrated more improvement in NOSPECS and scores of ocular motility. Orbital, EOM, and fat volume significantly decreased in the SRT group; however, only fat volume was reduced in the ST group. Compressive optic neuropathy after treatment developed in 0 % of the SRT group and 3.4 % (2/59) of the ST group. Reactivation of inflammation occurred in 11.8 % (8/68) of the SRT group and 28.8 % (17/59) of the ST group. CONCLUSIONS: Orbital radiotherapy in combination with steroid treatment significantly improved ocular motility by reducing EOM volume in patients with active GO.

Lateral Canthal Position Following Lateral Orbitotomy and the Influence of Ocular Proptosis.

PURPOSE: Anecdotal evidence suggests that detachment of the lateral canthal tendon during lateral orbitotomy results in shortening of the horizontal palpebral aperture (HPA) and rounding of the lateral canthal angle (LCA). This study investigated the change in HPA and LCA following lateral orbitotomy and the effect of proptosis on the HPA. METHODS: Retrospective, single surgeon, review of all cases undergoing lateral orbitotomy, comprising of a canthotomy and cantholysis and reconstruction of the lateral canthus using a single suture. The HPA and lateral canthal height (LCH) were measured on pre- and postoperative photographs using ImageJ software. Changes in the LCA and degree of proptosis were also investigated. Exclusion criteria included previous eyelid surgery, acute trauma, and less than 6 months' follow up. RESULTS: There were 41 cases of lateral orbitotomy in 27 patients, 67% female, average age 51 years. Twenty patients had thyroid eye disease of which 14 underwent bilateral surgery; the other 7 patients had a variety of orbital pathologies. Thirteen patients underwent unilateral orbitotomy with the contralateral eye serving as a control. Average follow up was 23 months. Overall, the HPA and proptosis were reduced by 0.6 mm (p = 0.143) and 3.4 mm (p < 0.001), respectively. A 0.2-mm reduction in HPA was observed for every 1-mm reduction in proptosis. A difference in post-orbitotomy HPA was observed between cases and their matched controls (p = 0.016). No rounding of the LCA or significant change in LCH was observed following lateral orbitotomy. CONCLUSIONS: The described technique of lateral orbitotomy and simple reconstruction do not appear to cause lateral canthal drift or rounding. There was no significant change in HPA or LCH. The degree of change of proptosis does appear to influence the change of HPA.