Methotrexate as an Adjuvant in Severe Thyroid Eye Disease: Does It Really Work as a Steroid-Sparing Agent?

PURPOSE: To compare the efficacy and safety of adjunctive oral methotrexate with intravenous pulsed methylprednisolone against methylprednisolone alone in the treatment of severe thyroid eye disease. METHODS: Retrospective review of clinical data of patients with severe sight-threatening thyroid eye disease with compressive optic neuropathy treated with methylprednisolone with and without methotrexate. Eye disease outcome measures (e.g., VISA inflammatory score and vision) at 0, 3, 6, 12, and 18 months were recorded. RESULTS: There were 72 subjects including 33 who had methylprednisolone alone and 39 with methylprednisolone with methotrexate. There were no statistical differences in demographics and baseline measures of disease activity or vision between the 2 treatment groups. No significant statistical differences in the cumulative dosage of methylprednisolone or occurrence of restrictive myopathy, raised intraocular pressure, proptosis, and exposure keratopathy between the groups at 0, 3, 6, 12, and 18 months were found. However, subjects who received methylprednisolone with methotrexate had better visual acuity of more than 2 lines on Snellen chart (p = 0.026) and VISA inflammatory score (p = 0.034) at 3 months, but no differences at 6, 12, and 18 months. Three patients who received methylprednisolone with methotrexate had transient worsening of liver function. No patient developed severe adverse reaction. CONCLUSIONS: The results demonstrated improved vision and disease activity at 3 months in the combination treatment group. This may suggest that the addition of methotrexate to methylprednisolone is beneficial for accelerating suppression of disease activity and hastens visual recovery. Addition of methotrexate to methylprednisolone did not reduce the requirement for steroids.

Clinical Features and Treatment Outcomes of Orbital Inflammatory Disease in Singapore: A 10-Year Clinicopathologic Review.

PURPOSE: 1) To assess the clinical profile and treatment outcomes of orbital inflammatory disease in the local population, and 2) classify patients using current histopathological criteria. METHODS: Ten-year retrospective clinicopathologic review of patients diagnosed with orbital inflammatory disease who underwent tissue biopsy from January 2001 to December 2011 at a tertiary referral centre in Singapore. Data collection included patient demographics, clinical presentation, investigations, systemic disease, histopathology review, clinical classification, medical and surgical management, response to treatment and recurrence rates. RESULTS: The study comprised 70 patients. Thirty-seven (52.9%) had nonspecific inflammation distributed as follows: lacrimal (n = 23), diffuse (n = 5), anterior (n = 5), myositic (n = 4). Thirty-three (47.1%) had specific inflammation of the following subtypes: idiopathic sclerosing inflammation (n = 9), granulomatous disorders (n = 8), transitional lesions (n = 5), vasculitis (n = 4), and others (n = 7). A total of 76.8% of patients received oral prednisolone, with a median duration of three months. Response to treatment was good in 71.9% of patients. Recurrence occurred in 22 (32.8%) patients at a mean interval of 20 months after completion of treatment, and was higher in myositic and vasculitic subtypes. There was no significant correlation between duration of treatment and recurrence. CONCLUSIONS: This study has re-emphasized the importance and utility of orbital biopsy and histopathologic typing for optimal management of orbital inflammatory disease. It has also improved the knowledge of the rate and response to treatment of its various subtypes.

Orbital inflammatory disease in relapsing polychondritis.

We present a 73-year-old Chinese male with bilateral relapsing, remitting orbital inflammatory disease associated with relapsing polychondritis. He first presented with right orbital inflammation that did not improve despite antibiotic treatment. Computer tomography (CT) of the orbits showed a soft tissue mass along the roof of the orbit, which was biopsied, revealing acute on chronic inflammation. There was complete resolution of his orbital inflammation within 2 weeks of initiating systemic steroid treatment. He subsequently developed recurrent bouts of left orbital inflammation. One year later, he was diagnosed with relapsing polychondritis and subsequently developed multiple myeloma seven years later. Comanagement with a rheumatologist will be helpful to achieve control of the disease with judicious use of immunosuppression. Long-term follow-up of the patient will be necessary to monitor for malignant transformation of the orbital lesion, as well as the development of other hematologic malignancies.

Prospective audit of ptosis surgery at the Singapore National Eye Centre: two-year results.

PURPOSE: To evaluate the demographics, presentation, and surgical outcomes of patients undergoing ptosis surgery in an Asian population in a prospective manner. METHODS: A prospective ptosis audit was conducted over a 2-year period from January 2010 to December 2011 in a tertiary eye hospital in Singapore. All patients undergoing ptosis surgery by, or under the supervision of, an oculoplastic-trained consultant in the institution were included. Institutional Review Board approval was obtained for the study. RESULTS: This study comprises 302 patients, of which 236 were acquired and 66 were congenital ptosis cases. Levator repair (77.2%) was the most commonly performed procedure, followed by levator resection (13.9%) and brow suspension (8.9%). Forty-seven (10.1%) eyes had readjustment within 2 weeks, the reasons for readjustment being eyelid height undercorrection (n = 35), eyelid height overcorrection (n = 9), and unsatisfactory eyelid contour (n = 4). Postoperatively, 93.8% of patients showed an increase in marginal reflex distance-1 (MRD1), 91.3% achieved symmetry or <1 mm of asymmetry in MRD1, 98.5% had good eyelid contour, and 74.3% had symmetric eyelid crease. On a scale of 1 to 10, 83.1% of patients gave a subjective grade of 7 or better. CONCLUSIONS: This study is the first prospective ptosis surgery audit in an Asian population and takes a leading step in assessing both subjective and objective surgical outcomes in a prospective manner. With the continuation of this audit in years to come, it will allow us to generate clinical outcomes in a robust manner and allow for more reliable benchmarking with major centers elsewhere.

A survey of the histopathology of lacrimal gland lesions in a tertiary referral centre.

PURPOSE: To describe the histopathological distribution of biopsied lacrimal gland lesions in a tertiary referral centre in Singapore. METHODS: This was a retrospective chart review. Clinical records of patients who underwent lacrimal gland biopsy at a tertiary referral centre in Singapore between 2000 to 2010, were reviewed. Data collated included patient demographics, clinical presentation, association with systemic disease and histopathological diagnosis. RESULTS: Sixty-nine patients were studied. Median age of presentation was 50 years. Forty patients (58%) were female and the majority (84%, n = 29) were Chinese. The mean follow-up duration was 35.0 ± 34.5 months. 30.4% (n = 21) of the patients had bilateral disease. Chronic dacryoadenitis (46%, n = 32) was the most common histopathological diagnosis, followed by lymphoproliferative disorders (38%, n = 26) and pleomorphic adenoma (10%, n = 7). The diagnoses in four other patients included adenoid cystic carcinoma, lacrimal gland hypertrophy, lacrimal duct cyst and orbital vascular malformation. CONCLUSION: Chronic dacryoadenitis and lymphoproliferative disorders are the two commonest causes of lacrimal gland lesions in our series. Although many cases remain non-specific, about 60% have a specific inflammation that may be associated with a systemic disease. As one third of our patients with lymphoproliferative disease of the lacrimal gland had an associated systemic lymphoma, patients with such lesions should be referred for investigation of possible systemic lymphoma. The results of our study can aid in providing a more targeted approach to patient management.

A 5-year retrospective review of Asian ectropion: how does it compare to ectropion amongst non-Asians?

INTRODUCTION: This study reviews the differences in demographics and surgical outcomes between ectropion in Asian and non-Asian eyes. MATERIALS AND METHODS: Medical records of surgically corrected ectropion cases from January 2002 to December 2006 were reviewed. Preand postoperative lid-globe apposition was graded: grade 0 with normal lid-globe apposition, grade 1 with punctal ectropion, grade 2 with partial lid eversion and scleral show, grade 3 with conjunctival hyperemia and thickening and grade 4 as for grade 3 with exposure keratitis. RESULTS: Sixty-nine eyes in 50 patients underwent surgical correction of lower lid ectropion, making up 3.3% of all lid procedures performed. Eighty-four percent of patients were above 50 years of age, 72% were males and 88% were Chinese. Involutional change was the commonest aetiology, accounting for the majority of bilateral cases. The mean duration to surgery was 10.0 ± 16.0 months. The most frequent preoperative severity grade was 2. Lateral tarsal strip (LTS) was the commonest procedure performed, comprising 91.3% of eyes. The mean duration of postoperative review was 19.4 ± 19.2 months (range, 1 to 74 months). Postoperative improvement of at least one grade was observed in 98% while normal lid-globe apposition was achieved in 76% of eyes. CONCLUSIONS: Involutional change is the most common cause of ectropion amongst both Asians and non-Asians. Ectropion is less prevalent amongst Asians as a result of anatomical differences and possibly reduced sun exposure. The LTS procedure is the most commonly performed surgical procedure for the successful correction of ectropion in both Asians and non-Asians.

Bilateral Kuttner tumours of the lacrimal glands.

Kuttner Tumour is a chronic inflammatory disease diagnosed histologically. It is under-diagnosed due to lack of awareness of the disease. We present a case of a 40-year old female with recurrent upper lid swelling. Biopsy revealed the diagnosis of Kuttner Tumours of the lacrimal glands. Although surgical excision is a treatment option, it can be treated with a course of steroids. Our patient opted for conservative management. We describe the presentation and course of the case, with an emphasis on the histological features of the tumour.

Asian blepharoplasty--an overview.

Asian blepharoplasty has evolved over the years as greater understanding of the differences between the Asian and Caucasian eyelid anatomy has led to the development of modified techniques for upper lid blepharoplasty. The aim of Asian upper blepharoplasty is to create a pleasing and permanent upper lid crease. This article reviews the differences in the anatomy and the various techniques currently employed.

Medial pretarsal adipose tissue in the Asian upper eyelid.

PURPOSE: To report the presence of a localized pad of adipose tissue in the medial anterior tarsal surface of the Asian upper eyelid. METHODS: Clinicohistologic case series. The presence and extent of a localized pad of adipose tissue in the medial pretarsal area were documented: 1) intraoperatively for 51 consecutive upper eyelid surgeries; and 2) in the histologic study of 10 cadaveric upper eyelid specimens. RESULTS: Medial pretarsal adipose tissue, ranging from 5 mm to 22 mm in size, was consistently found in all clinical patients regardless of age, gender, ethnicity, or underlying pathology. Histologic examination of the cadaveric specimens confirmed the presence of a localized pad of adipose tissue on the anterior surface of the superior tarsus medially. CONCLUSIONS: The presence of a localized pad of adipose tissue on the anterior surface of the medial superior tarsus seems to be a consistent finding in Asians.

Orbital cysts lined with both stratified squamous and columnar epithelia: a late complication of silicone implants.

Two patients presented with orbital cysts 5 and 7 years after orbital blowout fracture repair with silicone plate implants. The orbital cysts caused significant exophthalmos and restriction in ocular motility. Surgical excision revealed thick-walled cysts that were displacing the globe and encapsulating the silicone implant. On histopathologic examination, the cysts were lined with both stratified squamous and ciliated columnar (respiratory) epithelia. We propose that squamous and respiratory epithelial cells may have been deposited during surgery from the conjunctival and sinus epithelia, respectively. This case series illustrates that although an uncommon complication, epithelium-lined inclusion cysts may develop several years after orbital fracture repair with a silicone implant. A transconjunctival surgical approach is a possible risk factor.

Microscopic anatomy of the lower eyelid in asians.

PURPOSE: To study the microscopic anatomic relation of the capsulopalpebral fascia, orbital septum, and tarsus of the lower eyelid in Asians. The anatomic differences between the Asian and non-Asian upper eyelid have been well described by various authors, but the differences of the lower eyelid have not been well characterized microscopically. The microscopic anatomy of the lower eyelid in non-Asians was well studied, but in Asians, despite the presence of gross differences, there were very limited studies on the microscopic anatomy. A thorough knowledge of the Asian lower eyelid anatomy is essential for surgical exploration of the eyelid. It may also explain the higher prevalence of eyelid disorders such as epiblepharon and entropion in Asians. METHODS: Ten normal Asian lower eyelids from 10 formalin-fixed cadavers (mean age, 67.5 years) were harvested and studied with light microscopy after staining with Masson trichrome. RESULTS: There was no fusion of the orbital septum and the capsulopalpebral fascia at the lower border of the tarsal plate in 7 specimens and a very limited fusion of these tissues in 3 specimens. The average distance from the inferior tarsal border to the first observable smooth muscle nuclei of the inferior retractors was 1.44 mm. The average tarsal plate thickness was 1.36 mm and the average tarsal plate height was 4.12 mm. CONCLUSIONS: The Asian lower eyelid anatomy differs from its non-Asian counterpart. There was no consistent fusion between the capsulopalpebral fascia and the orbital septum inferior to the inferior tarsal border. No extension of the capsulopalpebral fascia to the skin was observed. The average distance between the inferior retractors and the inferior tarsal plate was 1.44 mm in the normal Asian lower eyelid.

Orbital, adnexal, and unusual systemic involvement in Rosai-Dorfman disease.

PURPOSE: To describe the unusual clinical course of a patient with Rosai-Dorfman disease (RDD) affecting the eyelid and orbital tissues and involving the spinal cord. METHODS: Case report. RESULTS: A 68-year-old Indian man first presented in 1994 with a right lower eyelid lump for 1 year. An en bloc excisional biopsy was reported to show "reactive lymphoid hyperplasia with sclerosis." The patient subsequently defaulted follow-up and presented again in 1999 with bilateral lower eyelid masses and proptosis. Computerized tomography showed bilateral orbital, ethmoidal sinus, and frontal sinus soft tissue masses. Bilateral excisional biopsies of the orbital and eyelid masses showed histologic features of RDD. The patient had a history of paraplegia with decompression laminectomy and excision of an epidural mass in 1994. In addition, he underwent excision of soft tissue masses from the abdominal wall in 1993. Retrospective review of the histologic specimens from these two areas showed a histologic picture similar to that of eyelid specimens (in 1994 and 1999). CONCLUSIONS: It is important to consider RDD in addition to lymphoproliferative disorders in a patient with orbital and ocular adnexal masses. The initial histologic presentation may not be pathognomonic.